bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal study of platelet angiotensin II binding in human pregnancy
Authors: Baker Philip N. , Pipkin Fiona Broughton , Symonds E. Malcolm
Published: August 2015

1. Platelet angiotensin II binding, circulating angiotensin II levels, plasma renin substrate and plasma renin concentration were measured in a longitudinal study of 30 women during pregnancy and the puerperium.

2. There was a significant fall in platelet angiotensin II binding from 11 weeks gestation to 18 weeks gestation (P < 0.01). There were no further significant changes in platelet angiotensin II binding until after delivery, a significant rise in platelet angiotensin II binding being found at 6 weeks post partum as compared with at 36 weeks gestation (P < 0.01). There was no further significant change from 6 to 12 weeks post partum, and platelet angiotensin II binding at 6 and 12 weeks post partum in the pregnant cohort approximated to that in non-pregnant women. These changes parallel those known to occur in pressor responsiveness to angiotensin II in pregnancy.

3. Plasma angiotensin II concentration, plasma renin substrate and plasma renin concentration were all significantly higher during pregnancy than in the puerperium (P < 0.001). There were no significant changes during pregnancy in plasma angiotensin II concentration or plasma renin concentration, although plasma renin substrate rose throughout.

4. Significant inverse correlations between platelet angiotensin II binding and plasma angiotensin II concentration (P < 0.01), plasma renin substrate (P < 0.01) and plasma renin concentration (P 0>001) were found during pregnancy. These data suggest that down-regulation of platelet angiotensin II binding by the components of the renin-angiotensin system pertains in pregnancy.

5. We are currently investigating parallelism between platelet and vascular angiotensin-binding sites. If such is confirmed, studies of platelet angiotensin II binding in pregnancy may be of both basic physiological and clinical interest in relation to the hypertensive diseases of pregnancy.
Dose-response study of the redistribution of intravascular volume by angiotensin II in man
Authors: Motwani Joseph G. , Struthers Allan D.
Published: August 2015

1. The response of systemic and regional haemodynamic indices to increasing infusion rates of angiotensin II (1, 3 or 10 ng min−1 kg−1) or placebo [5% (w/v) d-glucose] was studied in eight normal male subjects.

2. As compared with placebo, angiotensin II infusion caused an incremental rise in the serum angiotensin II level [14.5 ± 7.7 (placebo) to 187.2 ± 36.1 (10 ng of angiotensin II min−1 kg−1) pmol/l; mean ± 95% confidence interval] associated with a stepwise increase in total peripheral resistance [880 ± 42 (placebo) to 1284 ± 58 (10 ng of angiotensin II min−1 kg−1) dyn s cm−5] and a progressive reduction in cardiac output [8.3 ± 0.4 (placebo) to 7.0 ± 0.4 (10 ng of angiotensin II min−1 kg−1) litres/min].

3. A stepwise fall in renal blood flow was observed with increasing angiotensin II infusion rate [1302 ± 65 (placebo) to 913 ± 64 (10 ng of angiotensin II min−1 kg−1) ml/min]. In contrast, calf blood flow was unaffected by 1 ng or 3 ng of angiotensin II min−1 kg−1 and was significantly increased by 10 ng of angiotensin II min−1 kg−1 (P < 0.01).

4. Calf venous capacitance was uninfluenced by 1 ng of angiotensin II min−1 kg−1, but was significantly increased by both 3 ng (P < 0.005) and 10 ng (P < 0.001) of angiotensin II min−1 kg−1.

5. Our results indicate that the pressor response to angiotensin II is a summation of multiple regional haemodynamic effects which differ qualitatively not only with the vascular bed studied but also within a single tissue, with the level of circulating angiotensin II attained.

6. The venodilatation we have demonstrated with high angiotensin II levels may effect a potentially favourable redistribution of blood flow in situations of inappropriate extracellular fluid volume expansion, such as chronic heart failure.
Effect of oral lithium on bronchial reactivity in asthma
Authors: Knox A. J. , Higgins B. G. , Hall I. P. , Tattersfield A. E.
Published: August 2015

1. Recognition that inositol phospholipid-derived second messengers are involved in the initiation and maintenance of airway smooth muscle contraction raises the possibility of new therapeutic approaches to the treatment of asthma. We anticipated that lithium, through its effects on cell signal transduction and ion-transport pathways, would be likely to protect the airways against constrictor stimuli.

2. We carried out a randomized, double-blind study of lithium carbonate in asthmatic patients.

3. After a 1 week run-in period, 27 patients were allocated lithium carbonate (800 mg) or placebo for 21 days with measurement of forced expiratory volume in 1 s, the dose of histamine causing a 20% fall in the forced expiratory volume in 1 s and serum lithium concentration on days 3, 7, 14 and 21.

4. Twenty-one patients completed the study (10 on lithium, 11 on placebo). Mean serum lithium levels for patients on active treatment were in the therapeutic range on all four occasions.

5. Lithium did not alter the forced expiratory volume in 1 s (P=0.8) or the twice-daily peak expiratory flow (P=0.15). It did, however, reduce histamine reactivity (the maximum difference between lithium and placebo was 1.2 doubling doses of histamine on day 21; 95% confidence interval 0.2–2.2 doubling doses), improve symptom scores (P < 0.05) and reduce usage of β-adrenoceptor agonist inhalers (P < 0.05).

6. We conclude that lithium reduces bronchial reactivity in airway smooth muscle; this finding raises new therapeutic possibilities for the treatment of asthma.
Effects of xylitol- and/or glutamine-supplemented parenteral nutrition on septic rats
Authors: Salleh M. , Ardawi M.
Published: August 2015

1. The effects of parenteral nutrition with or without xylitol and/or glutamine supplementation were studied in septic rats after 4 days of treatment.

2. Septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition survived sepsis significantly better than other parenteral nutrition-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with xylitol-glutamine-supplemented parenteral nutrition was 9.5% compared with 54.5% in septic rats given parenteral nutrition without xylitol and glutamine, and 52.4% in septic rats treated with parenteral nutrition supplemented with glucose.

3. Xylitol- and/or glutamine-supplemented parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was positive in the rats given xylitol-supplemented parenteral nutrition and more positive when rats were treated with xylitol-glutamine-supplemented parenteral nutrition, as compared with other groups of septic rats.

4. The rate of loss of intracellular glutamine in skeletal muscle was markedly decreased (P < 0.001) in response to xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats.

5. Hepatic protein and RNA contents were increased in septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition. Similarly, protein and RNA contents were markedly increased in muscles of septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition.

6. The rates of incorporation of leucine/tyrosine into liver/muscle proteins in vitro were increased and the rate of muscular tyrosine release was decreased in response to xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats.

7. It is concluded that the administration of xylitol- and/ or glutamine-supplemented parenteral nutrition is beneficial to septic rats and possibly to septic patients.
Effects of oral contraceptives containing oestrogen combined with norethisterone or levonorgestrel on erythrocyte cation transport in normal women
Authors: Stokes G. S. , Monaghan J. C. , Flemming C. L. , Johnston H. , Jones M. , Pinkerton G. , Baber R.
Published: August 2015

1. Studies were undertaken in pre-menopausal women to examine the effects of treatment with standard oestrogen-progestogen and progestogen-only oral contraceptives on erythrocyte Na+,K+ co-transport and Na+−Na+ countertransport over 3- and 6-month periods. Concurrent observations were made on other erythrocyte cation transport components, plasma lipid concentrations, plasma renin activity, plasma aldosterone concentration and blood pressure.

2. Na+,K+ co-transport, measured as the ouabain-resistant, frusemide-sensitive component of 86Rb+ influx, and Na+−Na+ countertransport, measured as the ouabain-resistant, phloretin-sensitive component of 22Na+ influx, were both increased in women taking, on days 1–21 of their cycle, ethinyloestradiol (30–50 μg) combined with norethisterone (1000 μg or 500–1000 μg) for 3 or 6 months. Neither of these fluxes was increased in a control group of women, or in women treated for the same time periods with ethinyloestradiol combined with levonorgestrel.

3. In a separate study of erythrocyte cation transport (excluding Na+−Na+ countertransport), in which women undertook treatment with norethisterone only (350 μg/ day) for 6 months starting 6 weeks post partum, no changes in Na+,K+ co-transport were observed at 3 or 6 months; there were no changes in cation transport in a corresponding control group.

4. The results of these studies confirm that certain oral contraceptive compounds can alter erythrocyte cation transport, and indicate that norethisterone in higher dose preparations is the component predominantly responsible. The alterations observed could not be explained by a direct link with concurrent changes in plasma triacylglycerol concentrations or in the renin-aldosterone axis and were not closely associated with elevation of blood pressure.
Lithium pretreatment affects renal and systemic responses to angiotensin II infusion in normal man
Authors: Eadington D. W. , Freestone S. , Waugh C. J. , Swainson C. P. , Lee M. R.
Published: August 2015

1. Renal and systemic responses to infusion of angiotensin II (1.25 and 2.5 ng min−1 kg−1 body weight) were examined in ten normal males 12 h after single doses of 750 mg of lithium carbonate, 250 mg of lithium carbonate (n = 6) or placebo.

2. Baseline mean arterial pressure [mean (sem)] was higher after 750 mg of lithium [93.1 (1.7) versus 89.5 (1.9) mmHg, P = 0.014], and the subsequent rise in blood pressure during angiotensin II infusion was lower [8.2 (1.8) versus 12.2 (2.4) mmHg, P < 0.02].

3. Lithium at a dose of 750 mg increased overnight urinary sodium excretion before the study. The fall in fractional sodium excretion during angiotensin II infusion was reduced after pretreatment with 750 mg of lithium [750 mg of lithium, 2.73 (0.24) to 1.34 (0.08)%; placebo, 2.69 (0.26) to 1.01 (0.11)%; P=0.02]. The increases in effective filtration fraction [750 mg of lithium, 5.4 (1.0)%; placebo, 8.6 (0.7)%; P < 0.05] and total effective renal vascular resistance [750 mg of lithium, 3700 (390) dyn s cm−5; placebo 5100 (460) dyn s cm−5; P=0.03] during angiotensin II infusion were also attenuated after 750 mg of lithium. Responses after 250 mg of lithium did not differ from those after placebo.

4. The fall in plasma renin activity and the increase in plasma aldosterone concentration during angiotensin II infusion were similar on each study day.

5. Renal responses to exogenous angiotensin II are altered after pretreatment with a 750 mg dose of lithium in normal man. This dose of lithium is not an inert marker of sodium handling.
Altered renal response to enhanced endogenous 5-hydroxytryptamine after tryptophan administration in essential hypertension
Authors: Tomoda Fumihiro , Takata Masanobu , Oh-Hashi Shinya , Ueno Hitoshi , Yasumoto Kotaro , Iida Hiroyuki , Sasayama Shigetake
Published: August 2015

1. To examine the pathophysiological significance of 5-hydroxytryptamine (serotonin) in essential hypertension, we compared the renal response to intrarenally formed 5-hydroxytryptamine by oral dosing with its precursor, L-tryptophan (2 g), in nine patients with essential hypertension and in six subjects with normotension.

2. Before tryptophan administration, urinary excretion of 5-hydroxytryptamine was significantly higher in the hypertensive group than in the normotensive group (66 ± 8 versus 36 ± 6 ng/min, P < 0.05), whereas renal plasma flow and glomerular filtration rate did not differ between the two groups. After dosing with tryptophan, urinary excretion of 5-hydroxytryptamine significantly increased to the same plateau level in both groups (366 ± 55 ng/min in the hypertensive group and 365 ± 64 ng/min in the normotensive group). Significant and equivalent decreases in renal plasma flow were observed in the early phase after tryptophan administration in both groups (−8.5 ± 3.4% in the hypertensive group and −8.2 ± 1.7% in the normotensive group). Thereafter, renal plasma flow increased to above the baseline value in normotensive subjects, whereas this late vasodilatation was absent in the hypertensive group. Glomerular filtration rate significantly decreased at the time of the fall in renal plasma flow in the normotensive group (106.8 ± 7.8 to 92.7 ± 8.5 ml min−1 1.73 m−2, P < 0.05), whereas it remained unchanged in the hypertensive group (108.2 ± 6.2 to 110.4 ± 6.3 ml min−1 1.73 m−2, not significant). Consequently, the filtration fraction did not change in normotensive subjects (0.21 ± 0.01 versus 0.19 ± 0.01, not significant), but it increased significantly in the hypertensive group (0.22 ± 0.01 versus 0.26 ± 0.02, P < 0.05). A similar sustained antidiuresis was also observed after tryptophan administration in both groups. In addition, the above-described renal functional changes were not accompanied by any significant changes in systemic blood pressure, the renin-angiotensin-aldosterone system, adrenergic activity or plasma 5-hydroxytryptamine concentration in either group.

3. Our data show that in essential hypertension there is a baseline overproduction of renal 5-hydroxytryptamine, which may contribute to a reduction in renal excretory capability. The altered renal response to tryptophan found in essential hypertension may be partly related to the exaggerated efferent arteriolar constriction induced by endogenously formed 5-hydroxytryptamine.
Effect of bicarbonate administration on skeletal muscle intracellular pH in the rat: implications for acute administration of bicarbonate in man
Authors: Thompson Campbell H. , Syme Paul D. , Williams E. Mark , Ledingham John G. G. , Radda George K.
Published: August 2015

1. The effect of bicarbonate administration on the intracellular pH of rat skeletal muscle was examined by using 31P n.m.r.

2. Bicarbonate administered intraperitoneally caused a significant intracellular acidosis in rat skeletal muscle in vivo. When the bicarbonate was administered intravenously there was no such change in the pH of the skeletal muscle.

3. Bicarbonate administration by either route resulted in an elevated mixed venous partial pressure of carbon dioxide and an elevated arterial pH, but no significant change in the arterial partial pressure of carbon dioxide. The increase in arterial bicarbonate concentration after intraperitoneal injection of bicarbonate was delayed when compared with that after intravenous injection.

4. The administration of hypertonic solutions intravenously caused a transient 40–50% fall in blood pressure, which had resolved within 1 min.

5. The data suggest that the effect of bicarbonate administration on intracellular pH in vivo is related not only to carbon dioxide loading of the cell but also to the rate of change in the extracellular bicarbonate concentration.
Effects of epidermal growth factor and glutamine-supplemented parenteral nutrition on the small bowel of septic rats
Authors: Salleh M. , Ardawi M.
Published: August 2015

1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 μg/g body weight) was studied in the small bowel of septic rats after 4 days.

2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment.

3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats.

4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine (P < 0.001) and production of ammonia (P < 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment.

5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4–40.6%), DNA content (by 24.2–34.7%), protein content (by 29.1–50.0%), villus height (by 16.3–26.4%) and crypt depth (by 20.3–29.6%) compared with other groups of septic rats.

6. The rate of intestinal [3H]thymidine incorporation in vivo and thymidine kinase activity in vitro were significantly increased (P < 0.001) in septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor.

7. The activity of jejunal glutamine synthetase was lower (by 66.3–90.0%) in septic rats treated with glutamine, epidermal growth factor or glutamine and epidermal growth factor, whereas glutaminase activity was increased (by 28.1–31.0%) in response to parenteral nutrition supplemented with glutamine only.

8. It is concluded that the administration of glutamine-supplemented parenteral nutrition, with or without epidermal growth factor, is beneficial to the small bowel of septic rats.
Lithium clearance in dogs: effects of water loading, amiloride and lithium dosage
Authors: SHALMI Michael , Laursen Jørn Bech , Plange-RHULE Jacob , Christensen Sten , Atherton John , Bie Peter
Published: August 2015

1. The influences of lithium dosage, urine flow rate and acute administration of amiloride on the renal handling of lithium in normal conscious dogs were investigated.

2. Lithium was administered in the diet at daily doses of 100 mg or 2 mg of lithium carbonate for the 2 days preceding the investigation. Urine flow rate was altered by water loading with and without arginine vasopressin infusion (5 pg min−1 kg−1). Amiloride was administered as an intravenous bolus (130 μg/kg) followed by a continuous infusion (1.22 μg h−1 kg−1).

3. Glomerular filtration rate (exogenous creatinine clearance) did not change within series and was not different between series; it averaged 3.27 ml min−1 kg−1. Control levels of fractional lithium excretion (12.4 ± 1.2%, mean ± sem) were not influenced by hydration, hydration plus arginine vasopressin administration or the lithium dosage. However, in hydrated dogs having a plasma lithium concentration of 130–140 μmol/l, amiloride administration was associated with a 5% increase in fractional lithium excretion (P 0.01).

4. It is concluded that distal tubular lithium reabsorption may take place in sodium-replete conscious dogs undergoing water diuresis. The low fractional lithium excretion even during amiloride infusion (14.1–16.8%) may well be due to a high fractional reabsorption of lithium in the proximal tubules; however, a significant reabsorption of lithium distal to the proximal straight tubules by amiloride-insensitive pathways cannot be excluded.
Regional differences in the response to platelet-activating factor in rabbit colon
Authors: Travis S. P. L. , Jewell D. P.
Published: August 2015

1. Platelet-activating factor is an inflammatory mediator related to eicosanoids which is known to stimulate anion secretion in the distal colon. Since there are regional differences in ion transport within the colon, the influence of platelet-activating factors on ion transport and epithelial permeability has been studied in rabbit caecum and distal colon mounted in Ussing chambers.

2. The effect of platelet-activating factor (1–50 nmol/l) on net electrogenic ion transport was to stimulate a biphasic increase in short-circuit current in the distal colon but not in the caecum. The platelet-activating factor-induced rise in short-circuit current was shown by ion replacement and pharmacological inhibitor studies to be consistent with chloride and bicarbonate secretion in the early phase, but with chloride secretion alone in the later phase. The effect on ion transport was specific and reversible and was enhanced by 0.25% BSA.

3. Colonic permeability, assessed by transmucosal resistance and mannitol flux, was increased by platelet-activating factor in both the distal colon and the caecum. This was consistent with an effect on platelet-activating factor on the paracellular pathway, because resistance decreased even when transcellular chloride transport was inhibited by frusemide or ion replacement. A specific platelet-activating factor antagonist (U66985) inhibited the effects of platelet-activating factor in both the distal colon and the caecum.

4. The results show that platelet-activating factor stimulates anion secretion only in the distal colon, but increases permeability in both the caecum and the distal colon.
Influence of dietary protein on glomerular angiotensin II-receptor binding in normotensive and spontaneously hypertensive rats
Authors: Vaughan D. L. , Russell G. I.
Published: August 2015

1. The binding of angiotensin II to glomerular receptors was studied in spontaneously hypertensive and normotensive Wistar-Kyoto rats in response to 7, 16 and 32% isocaloric, isonatraemic protein diets.

2. Increased dietary protein elevated the systemic angiotensin II levels of both spontaneously hypertensive and Wistar-Kyoto rats [F0.05(2,26)=4.758, P<0.05; n=36], and this was not associated with changes in either systemic blood pressure or cortical renin activity.

3. Furthermore, no significant changes in the affinity or density of angiotensin II receptors were associated with changes of dietary protein intake in either strain.

4. These results indicate a dissociation between the systemic renin-angiotensin system and the tissue renin -angiotensin system in response to protein intake.
An automated computerized method using Finapres for measuring cardiovascular reflexes
Authors: Netten P. M. , Boots J. M. M. , Bredie S. J. H. , den Arend J. A. C. J. , Mol M. J. T. M. , Thien Th. , Hoefnagels W. H. L. , Lutterman J. A.
Published: August 2015

1. The major drawback of the cardiovascular reflex tests used to study autonomic failure is the time involved in calculating the results. To overcome this disadvantage, we have developed an automated computerized program using a FINger Arterial PRESsure instrument for the measurement of beat-to-beat heart rate and blood pressure on a finger.

2. This program calculates heart rate variability during three standardized tests, forced breathing, standing up and the Valsalva manoeuvre, and records blood pressure values in response to standing up and sustained handgrip. The time taken to perform the test and to calculate the results is usually 25 min.

3. The reproducibility of the tests in 21 normal subjects was comparable with the reproducibility obtained with conventional test methods using an ECG and a sphygmomanometer.

4. In addition, we determined the age-dependent normal values of the seven test parameters in 124 subjects aged 20–90 years.

5. Using this program in 10 patients with longstanding (14–50 years) complicated diabetes, in each of them four or more abnormal test results were found.
Platelets from patients on haemodialysis show impaired responses to nitric oxide
Authors: Gordge M. P. , Neild G. H.
Published: August 2015

1. Platelets from patients on haemodialysis showed a loss of sensitivity to nitric oxide, reflected by a reduction in the ability of nitric oxide both to inhibit thrombin-induced aggregation and to increase intraplatelet cyclic GMP levels. Responses of platelets from patients on continuous ambulatory peritoneal dialysis were slightly, but not significantly, impaired. Platelets from both groups of uraemic patients showed normal sensitivity to the cyclic AMP-dependent inhibitor prostacyclin.

2. Reduced levels of cyclic GMP in response to nitric oxide in platelets from patients on haemodialysis were due to a defect in its generation, rather than to accelerated breakdown.

3. Basal levels of intra-platelet cyclic GMP were significantly increased in both patients on haemodialysis and patients on continuous ambulatory peritoneal dialysis.

4. The activity of nitric oxide was more stable in plasma than in buffer; its survival in plasma from patients on haemodialysis was similar to that in plasma from healthy control subjects.
Reversal of extrahepatic membrane cholesterol deposition in patients with chronic liver diseases by S-adenosyl-l-methionine
Authors: Rafique Samina , Guardascione Marianna , Osman Elsir , Burroughs Andrew K. , Owen James S.
Published: August 2015

1. S-Adenosyl-l-methionine is reported to improve serum liver function tests in chronic liver disease. Because liver disease is complicated by cholesterol deposition in hepatic and extrahepatic membranes, we have assessed whether oral administration of S-adenosyl-l-methionine to patients with hepatic disease can reverse the cholesterol enrichment of their erythrocytes.

2. The mean erythrocyte cholesterol-to-phospholipid molar ratio in 13 jaundiced patients was reduced 2 weeks after oral administration of S-adenosyl-l-methionine (from 0.874 ± 0.112 to 0.844 ± 0.102, P<0.05) with 10 of the patients (77%) showing a decrease. By contrast, only four of 11 untreated patients (36%) had a reduced erythrocyte cholesterol-to-phospholipid molar ratio after 2 weeks and the mean values did not differ.

3. The plasma and erythrocyte cholesterol-to-phospholipid molar ratios remained closely correlated (r = 0.77, P<0.01) before and after treatment, suggesting that S-adenosyl-l-methionine had not acted directly on the cells but rather had improved their lipoprotein milieu. Further support for this concept was provided by following one patient, who initially failed to respond, during an additional 3 weeks of S-adenosyl-l-methionine administration. The plasma cholesterol-to-phospholipid molar ratio fell steadily from week 1 to week 5 and was accompanied by a progressive decrease in the erythrocyte cholesterol-to-phospholipid molar ratio. Moreover, the initially suppressed acetylcholinesterase activity of the erythrocyte membranes returned towards normal during this period.

4. This preliminary study is the first evidence in jaundiced patients that a drug can help to reverse the deposition of cholesterol in an extrahepatic membrane. It merits, therefore, placebo-controlled, crossover investigations into the therapeutic potential of S-adenosyl-l-methionine in chronic liver disease.
Vasopressin and angiotensin II in the conscious dog: synergistic effects on renal excretory parameters?
Authors: Eiken P. , Emmeluth C. , Schütten H. J. , Bie P.
Published: August 2015

1. The renal effects of angiotensin II were investigated (a) with and without acute blockade of the effects of aldosterone and (b) with and without concomitant infusion of vasopressin. Angiotensin II (2 ng min−1 kg−1) and/or vasopressin (5 pg min−1 kg−1) was infused intravenously into conscious water-diuretic dogs and the effects were quantified by measurements of renal excretion of water, Na+ and K+, as well as determination of plasma renin activity and plasma levels of atrial natriuretic peptide and catecholamines.

2. Angiotensin II alone increased blood pressure by 7% (P<0.05), decreased effective renal blood flow markedly and reduced urine flow and osmolar and free water clearances. Na+ and K+ excretion did not change significantly. Aldosterone blockade with canrenoate increased Na+ excretion by a factor of 10; subsequent infusion of angiotensin II decreased Na+ excretion by about 50%, the other renal effects being qualitatively similar to those seen without blockade. As expected, vasopressin also decreased diuresis and free water clearance substantially; however, the effect of combined infusion of angiotensin II and vasopressin was not compatible with the notion of additive effects of the two peptides.

3. Angiotensin II alone or in combination with vasopressin did not change the plasma concentrations of atrial natriuretic peptide, adrenaline, noradrenaline, or dopamine. Vasopressin alone exerted its antidiuretic effect without affecting plasma renin activity, plasma aldosterone concentration or renal excretion of Na+ and K+.

4. It is concluded that the antinatriuretic effect of angiotensin II is markedly dependent on the preexisting rate of Na+ excretion and that it is not possible to detect a persisting antidiuretic effect of angiotensin II in conjunction with the antidiuretic action of a moderate dose of vasopressin.
Platelet-activating factor causes hypoketonaemia in starved rats
Authors: Hiraide Atsushi , Evans Rhys D. , Williamson Dermot H.
Published: August 2015

1. The aim of this work was to examine whether platelet-activating factor could mimic the hypoketonaemia seen in septic and endotoxic experimental animals. Platelet-activating factor was administered either by the intraperitoneal (high dose) or intravenous (jugular vein, low dose) routes.

2. Intraperitoneal injection of platelet-activating factor (25 μg/kg body weight) decreased the blood ketone body concentration (acetoacetate plus 3-hydroxybutyrate) transiently (30 min after injection) in starved rats. Continuous intravenous infusion of platelet-activating factor (40 ng min−1 kg−1 for 5 h) caused comparable hypoketonaemia.

3. The hepatic acetoacetate concentration also decreased transiently after injection of platelet-activating factor and there was an increase in the 3-hydroxybutyrate/acetoacetate ratio. The hepatic ATP concentration decreased at 15 and 30 min after injection of platelet-activating factor. Infusion of platelet-activating factor caused a similar decrease in hepatic ketone body concentration, but no significant change in the 3-hydroxybutyrate/acetoacetate ratio or adenine nucleotide concentrations.

4. Platelet-activating factor administered by infusion, but not by injection, decreased the plasma non-esterified fatty acid concentration. The plasma glycerol concentration also decreased after infusion of platelet-activating factor, suggesting decreased lipolysis in adipose tissue.

5. Changes in plasma insulin concentration or white adipose tissue blood flow did not appear to contribute to the decrease in the plasma non-esterified fatty acid concentration after infusion of platelet-activating factor. However, there was a significant decrease in blood flow to interscapular brown adipose tissue in both the infused and injected groups.

6. These findings suggest that infusion of platelet-activating factor causes a decrease in ketone bodies by limiting the supply of non-esterified fatty acids to the liver, and that the transient hypoketonaemia seen with intraperitoneal injection may possibly be due to decreased oxidation of non-esterified fatty acids secondary to hepatic vasoconstriction.
Elevated levels of brain natriuretic peptide in acute hypoxaemic chronic obstructive pulmonary disease
Authors: Lang Chim C. , Coutie Wendy J. , Struthers Allan D. , Dhillon D. Paul , Winter John H. , Lipworth Brian J.
Published: August 2015

1. Studies in vitro have recently shown that both atrial natriuretic peptide and brain natriuretic peptide have pulmonary vasorelaxant activity. The purpose of the present study was to evaluate for the first time whether plasma levels of brain natriuretic peptide are elevated in chronic obstructive pulmonary disease. Plasma levels of brain natriuretic peptide and atrial natriuretic peptide were therefore measured in 12 patients admitted with acute hypoxaemic chronic obstructive pulmonary disease [arterial partial pressure of O2, 6.2 ± 0.4 kPa; arterial partial pressure of CO2, 6.9 ± 0.1 kPa; forced expiratory volume in 1 s, 0.6 ± 0.07 litre (27 ± 3% of predicted)]. All but three patients had oedema on admission.

2. Plasma levels of both brain natriuretic peptide and atrial natriuretic peptide were elevated in patients with chronic obstructive pulmonary disease (31.4 ± 4.1 pmol/l and 45.0 ± 8.1 pmol/l, respectively) compared with healthy control subjects (1.7 ± 0.8 pmol/l and 8.0 ± 3.5 pmol/l, respectively). Thus, plasma levels of brain natriuretic peptide and atrial natriuretic peptide in patients with chronic obstructive pulmonary disease were increased by 18.5- and 5.6-fold respectively compared with healthy control subjects.

3. There was a significant inverse correlation between the plasma level of brain natriuretic peptide and the arterial partial pressure of O2 (r = −0.65, r2 = 0.42, P = 0.03), but not between the plasma atrial natriuretic peptide level and the arterial partial pressure of O2 (r2 = 0.07, not significant). The arterial partial pressure of CO2 did not correlate with the plasma level of either brain natriuretic peptide or atrial natriuretic peptide.

4. Thus, plasma levels of brain natriuretic peptide were proportionately higher than those of atrial natriuretic peptide in patients with hypoxaemic chronic obstructive pulmonary disease. Unlike those of atrial natriuretic peptide, plasma levels of brain natriuretic peptide were correlated with the degree of hypoxaemia. Further studies are required to investigate the release and clearance of brain natriuretic peptide in chronic obstructive pulmonary disease, as well as its pulmonary vasodilator activity in vivo.
Metabolic clearance rate of arginine vasopressin in severe chronic renal failure
Authors: Argent Nicholas B. , Wilkinson Robert , Baylis Peter H.
Published: August 2015

1. The metabolic clearance rate of arginine vasopressin was determined using a constant infusion technique in normal subjects and patients with chronic renal failure immediately before commencing dialysis. Endogenous arginine vasopressin was suppressed in all subjects before the infusion with a water load.

2. Plasma arginine vasopressin concentrations were determined using a sensitive and specific radioimmunoassay after Florisil extraction. The detection limit of the assay was 0.3 pmol/l, and intra- and inter-assay coefficients of variation at 2 pmol/l were 9.7% and 15.3%, respectively.

3. In normal subjects, the metabolic clearance rate was determined at two infusion rates producing steady-state concentrations of arginine vasopressin of 1.3 and 4.4 pmol/l. In the patients with renal failure, a single infusion rate was used, producing a steady-state concentration of 1.5 pmol/l.

4. At comparable plasma arginine vasopressin concentrations, metabolic clearance rate was significantly reduced in patients with renal failure (normal 1168 ± 235 ml/min versus renal failure 584 ± 169 ml/min; means ± sd; P<0.001).

5. Free water clearance was significantly reduced in normal subjects during the arginine vasopressin infusion from 8.19 ± 2.61 to −1.41 ± 0.51 ml/min (P<0.001), but was unchanged in the patients with renal failure after attaining comparable plasma arginine vasopressin concentrations.

6. In normal subjects there was a small but significant fall in metabolic clearance rate at the higher steady-state arginine vasopressin concentration (1168 ± 235 ml/min at 1.3 pmol/l versus 1059 ± 269 ml/min at 4.4 pmol/l; P = 0.016).

7. Our results show that the metabolic clearance rate of arginine vasopressin is reduced by approximately 50% in severe chronic renal failure. This alone may account for the raised plasma concentrations of the hormone seen in this condition.
Weight loss normalizes the inhibitory effect of N6-(phenylisopropyl)adenosine on lipolysis in fat cells of massively obese human subjects
Authors: Ohisalo Jorma J. , Kaartinen Johanna M. , Ranta Susanna , Mustajoki Pertti , Hreniuk Stanely P. , LaNoue Kathryn F. , Martin Louis F.
Published: August 2015

1. Fat cells were isolated from massively obese patients at or before gastric bypass, from other patients after normalization of body weight after gastric bypass or gastroplasty (post-bypass patients) and from control subjects of a stable normal body weight.

2. The inhibition of isoprenaline-stimulated lipolysis by N6-(phenylisopropyl)adenosine in the presence of adenosine deaminase was much attenuated in cells from the massively obese patients as compared with those from normal-weight control subjects, but was normal in cells from post-bypass patients.

3. Isolated fat cells of the massively obese patients were larger (913 ± 197 pl, mean ± sem) than those of the normal-weight group (437 ± 95 pl). The volume of cells from the post-bypass patients was only 125 ± 49 pl, although the body mass index of this group was almost exactly the same as that of the normal-weight control subjects.

4. Although epidemiological studies have suggested that genetic factors are important in the development and maintenance of obesity, these results demonstrate that the changes observed in the inhibitory regulation of lipolysis in obesity are secondary.
Twenty-four hour C-peptide and insulin secretion rates and diurnal profiles of glucose, lipids and intermediary metabolites in cirrhosis
Authors: Kruszynska Yolanta T. , Munro Janet , Home Philip D. , McIntyre Neil
Published: August 2015

1. To examine the contributions of hypersecretion and decreased insulin clearance to the hyperinsulinaemia of cirrhosis, insulin secretion was calculated over the day from serum C-peptide concentrations and C-peptide metabolic clearance rate. The latter was measured during infusions of recombinant human C-peptide. In cirrhotic patients (n = 9) insulin secretion rate was twice that of normal control subjects (n = 10), both in the basal state [02.00–07.00 hours, 15.7 ± 2.1 (mean ± sem) nmol/h (2.6 ± 0.4 units/h) versus 7.0 ± 0.9 nmol/h (1.2 ± 0.2 units/h), P<0.002] and over 24 h [787 ± 93 nmol (132 ± 16 units) versus 346 ± 34 nmol (58 ± 6 units), P<0.001]. However, the area under the serum insulin concentration curve was approximately six times greater in the cirrhotic patients (24 h basal, 6.3 ± 1.0 versus 1.1 ± 0.31 nmol l−1 h, P<0.001; 24 h total, 21.7 ± 3.2 versus 3.7 ± 0.7 nmol l−1 h, P<0.001). Thus, despite impairment of insulin clearance there is continuing hyper-section of insulin in cirrhosis.

2. The relationship of carbohydrate and lipid metabolism with insulin secretion was assessed. In cirrhotic patients, 24 h blood glucose profiles showed a worsening of glucose tolerance over breakfast, despite greater insulin secretion compared with other meals, suggesting that the insulin insensitivity of cirrhosis is worse at this time.

3. Cirrhotic patients showed impaired suppression of blood glycerol levels after meals but normal suppression of serum non-esterified fatty acid concentrations. The greatest differences in the profiles of serum lipids and lipid-related metabolites in cirrhotic patients and control subjects occurred at night. Whereas in control subjects, serum non-esterified fatty acid, blood glycerol and blood 3-hydroxybutyrate concentrations peaked between 01.00 and 03.00 hours, falling gradually thereafter until 08.00 hours, in cirrhotic patients serum non-esterified fatty acid and blood glycerol levels showed a gradual increase during the night to reach maximal levels at 08.00 hours when they were twice those of control subjects (P<0.001).

4. The blood 3-hydroxybutyrate and serum triacyl-glycerol profiles suggested that in cirrhotic patients there was preferential utilization of non-esterified fatty acids for ketogenesis and reduced re-esterification to triacylglycerol.
Colonic absorption of human calcitonin in man
Authors: Antonin K. H. , Saano V. , Bieck P. , Hastewell J. , Fox R. , Lowe P. , MacKay M.
Published: August 2015

1. Human calcitonin was administered into the distal colon and by intravenous infusion in eight healthy subjects in an open, fixed sequence, cross-over bioavailability study.

2. Intravenously infused human calcitonin elicited a standard pharmacokinetic profile in eight healthy subjects with a biphasic elimination with half-lives of 10.2 ± 0.7 min and 37.8 ± 2.5 min.

3. Colonoscopically administered human calcitonin was absorbed across the distal colonic mucosa in low amounts with a bioavailability of 0.00–0.22%.

4. Absorption from the distal colon was impeded by the presence of faecal material in three of the eight subjects.

5. We conclude that human calcitonin crosses the gastrointestinal epithelium of man. This may demonstrate the feasibility of an oral form for clinical use.
α-Tocopherol, lipids and lipoproteins in knee-joint synovial fluid and serum from patients with inflammatory joint disease
Authors: Fairburn K. , Grootveld M. , Ward R. J. , Abiuka C. , Kus M. , Williams R. B. , Winyard P. G. , Blake D. R.
Published: August 2015

1. We have determined the antioxidant status of synovial fluid and serum of patients with inflammatory joint disease in terms of the biologically active lipid-soluble antioxidant, α-tocopherol. Synovial fluid concentrations of α-tocopherol were significantly lower relative to those of paired serum samples (P<0.001). Serum levels of α-tocopherol in these patients did not differ significantly from those in control serum.

2. Lower concentrations of cholesterol, triacylglycerol and low-density lipoprotein were also observed in patients' synovial fluid compared with matched serum samples. However, multiple regression analysis of the data indicated that there remained a significant depletion of α-tocopherol, which was largely independent of these co-variables, in inflammatory synovial fluid. These findings are consistent with the consumption of α-tocopherol within the inflamed joint via its role in terminating the process of lipid peroxidation.

3. Nuclear magnetic resonance spectroscopic analysis of matched inflammatory synovial fluid and serum confirmed lower concentrations of triacylglycerol in synovial fluid together with evidence of a shortened mean triacylglycerol chain length. The latter metabolic difference suggests an increased utilization of triacylglycerols for energy within the inflamed joint.
Effects of parathyroid hormone and calcium and their interrelationship on urinary acidification in the rat
Authors: Gil F. Zaladek , Silva V. L. Costa , Cavanal M. F. , Malnic G.
Published: August 2015

1. The influence of thyroparathyroidectomy on renal function and specifically on acid excretion was studied in rats with or without oral supplementation of calcium.

2. Thyroparathyroidectomy caused a significant decrease in glomerular filtration rate, in the urinary/ plasma inulin ratio and in overall acid excretion. These changes were not corrected by calcium supplementation.

3. Rates of proximal tubular acidification were studied by means of double-barrelled resin/reference microelectrodes. Acidification half-time was significantly increased in both thyroparathyroidectomized and calcium-supplemented thyroparathyroidectomized rats (838 s and 7.40 s, respectively) compared with control rats (5.44 s).

4. When 10−6 mol/l A23187, a calcium ionophore, was added to the luminal bicarbonate solution, the acidification half-time returned to 3.97 s in the thyroparathyroidectomized rats, whereas no significant changes were detected in the properties of acidification in the control rats.

5. These data show that parathyroid hormone and cellular calcium are important factors involved in proximal tubular H+ secretion, which appears to be largely dependent on a well-defined concentration range of these agents.
Aortic compliance in young patients with heterozygous familial hypercholesterolaemia
Authors: Lehmann E. D. , Watts G. F. , Fatemi-Langroudi B. , Gosling R. G.
Published: August 2015

1. Aortic compliance and plasma lipid and lipoprotein levels were measured in 20 young patients with heterozygous familial hypercholesterolaemia and in 20 age- and sex-matched control subjects.

2. Patients with familial hypercholesterolaemia had significantly higher plasma cholesterol, low-density lipoprotein-cholesterol and triacylglycerol levels than control subjects (P<0.001, P<0.001 and P<0.005, respectively). The patients with familial hypercholesterolaemia also had significantly more compliant (distensible) aortas than the control subjects (P<0.001), a significant inverse correlation being observed between compliance and age (r = −0.73, P<0.001) and between compliance and mean blood pressure (r = −0.60, P<0.005).

3. When the effects of age and sex on aortic compliance were corrected for, the blood pressure effect disappeared, significant correlations being observed between normalized compliance and cholesterol (r = 0.50, P<0.03), low-density lipoprotein-cholesterol (r = 0.54, P<0.01), high-density lipoprotein-cholesterol (r = −0.44, P<0.05), low-density lipoprotein-/high-density lipoprotein-cholesterol ratio (r = 0.60, P<0.006) and duration of disease (r = 0.67, P<0.002). Multivariate regression analysis showed that the low-density lipoprotein-/high-density lipoprotein-cholesterol ratio (P<0.03) and duration of disease (P<0.04) were the best predictors of normalized compliance.

4. We suggest that the measurement of aortic compliance in young patients with familial hypercholesterolaemia may potentially be a useful, noninvasive, research tool for assessing their susceptibility to atheroma.