bluuebunny/crossref_metadata_2025 huggingface dataset:
β
2-Adrenoceptor desensitization in cultured human airway smooth muscle
Authors: Hall Ian P. , Daykin Keri , Widdop Sophie
Published: August 2015

1. The mechanisms underlying control of cyclic AMP responses to isoprenaline were studied in primary cultures of human airway smooth muscle cells. In these cells, isoprenaline induced concentration-related cyclic AMP formation via β2-adrenoceptor stimulation.

2. Prior incubation of cells with varying concentrations of isoprenaline (1–16 h), forskolin, prostaglandin E2 or a stable analogue of cyclic AMP all produced concentration-related desensitization of cyclic AMP responses to subsequent challenge with isoprenaline (maximum reduction with 1 μmol/l isoprenaline, 85% after 16 h). The desensitization induced over 2 h (44%) by a concentration of prostaglandin E2 which gave a similar rise in cyclic AMP levels to 1 μmol/l isoprenaline was significantly less (P < 0.05) than the desensitization (62%) induced over 2 h by 1 μmol/l isoprenaline itself.

3. Isoprenaline-induced desensitization of β2-adrenoceptor-induced cyclic AMP formation was insensitive to prior exposure of cells to dexamethasone.

4. These findings suggest that isoprenaline-induced desensitization of β2-adrenoceptor-induced cyclic AMP formation in primary cultures of human airway smooth muscle cells is mediated through both a cyclic AMP-dependent and probably an additional cyclic AMP-independent pathway, and that these pathways are insensitive to inhibition by glucocorticoids.
Acute-phase protein response is impaired in severely malnourished children
Authors: Doherty J. F. , Golden M. H. N. , Raynes J. G. , Griffin G. E. , McAdam K. P. W. J.
Published: August 2015

1. The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children.

2. Sixty-six severely malnourished children were studied at admission. Fifty of these had clinical and/or laboratory evidence of infection. C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children.

3. Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. The first was given early in recovery, the second after nutritional rehabilitation. Ten mildly malnourished children acted as controls, receiving a single dose of diphtheria-pertussis-tetanus vaccine.

4. The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. The response of the mildly malnourished group was no different from that of the severely malnourished group in early recovery, but was less than their response on discharge.

5. The acute-phase protein response of malnourished children is impaired. This may have prognostic implications as the response plays a central role in promoting healing.
Non-insulin-mediated glucose uptake in human immunodeficiency virus-infected men
Authors: Heyligenberg R. , Romijn J. A. , Hommes M. J. T. , Endert E. , Schattenkerk J. K. M. Eeftinck , Sauerwein H. P.
Published: August 2015

1. One of the metabolic features of acquired immunodeficiency syndrome is increased tissue glucose uptake documented by euglycaemic-hyperinsulinaemic clamp studies, suggesting increased insulin sensitivity. However, these results may also be related to the confounding effect of increased non-insulin-mediated glucose uptake in acquired immunodeficiency syndrome, which will result in an erroneously presumed increased insulin sensitivity. To study the contribution of non-insulin-mediated glucose uptake to total tissue glucose uptake in acquired immunodeficiency syndrome, we conducted a hypoinsulinaemic clamp study in clinically stable human immunodeficiency virus-infected (Centers for Disease Control class IV) men (n = 7) and healthy subjects (n = 5). Glucose uptake was measured by a primed, continuous infusion of [3-3H]glucose in the postabsorptive state and during somatostatin-induced insulinopenia at euglycaemic (≈5.3 mmol/l) and hyperglycaemic (≈11 mmol/l) glucose concentrations.

2. Basal glucose concentration (patients, 5.2 ± 0.1 mmol/l; control subjects, 5.3 ± 0.1 mmol/l) and basal glucose tissue uptake (patients, 15.9 ± 0.5 μmol min−1 kg−1 fat-free mass; control subjects, 15.2 ± 0.4 μmol min−1 kg−1 fat-free mass) were not different between the two groups.

3. Euglycaemic glucose uptake during somatostatin infusion, reflecting non-insulin-mediated glucose uptake, decreased to 82 ± 3% in patients and 78 ± 2% in control subjects (not significant). Under hyperglycaemic (≈11 mmol/l) conditions with sustained insulinopenia, no differences in glucose uptake existed between the two groups (patients, 16.8 ± 0.6 μmol min−1 kg−1 fat-free mass; control subjects, 16.1 ± 0.3 μmol min−1 kg−1 fat-free mass).

4. Our results indicate that non-insulin-mediated glucose uptake is not increased in acquired immunodeficiency syndrome. Therefore the previously described increase in insulin sensitivity in acquired immunodeficiency syndrome during hyperinsulinaemia is explained by a real increase in insulin sensitivity and not by augmented non-insulin-mediated glucose uptake.
Cardiovascular responses to a high-fat and a high-carbohydrate meal in healthy elderly subjects
Authors: Sidery M. B. , Cowley A. J. , MacDonald I. A.
Published: August 2015

1. The cardiovascular responses to high-fat and high-carbohydrate meals (2.5 MJ) were compared in healthy, non-obese elderly subjects (mean age 68 years, range 63–74 years).

2. Measurements of cardiac output, blood pressure, heart rate, calf blood flow and superior mesenteric artery blood flow were made before and for 60 min after the two meals.

3. Systolic blood pressure only fell after the high-carbohydrate meal, reaching a nadir 13 mmHg below baseline values (95% confidence interval of the change, −2 to −25 mmHg). Diastolic blood pressure fell by 8 mmHg at 30 min after the high-carbohydrate meal (95% confidence interval of the change, −1 to −15 mmHg) and by 5 mmHg 45 min after the high-fat meal (95% confidence interval of the change, −1 to −8 mmHg).

4. Superior mesenteric artery blood flow rose by 70% after the high-carbohydrate meal (95% confidence interval of the change, +105 to +297 ml/min) and by 42% after the high-fat meal (95% confidence interval of the change, +35 to +256 ml/min, P <0.0001, analysis of variance). Calf blood flow reached a nadir 30 min after the high-carbohydrate meal (95% confidence interval of the change, −0.14 to −0.96ml min−1 100 ml−1) and 15min after the high-fat meal (95% confidence interval of the change, −0.1 to −0.92ml min−1 100ml−1P <0.01). There was no significant change in heart rate or cardiac output over the experimental period.

5. In elderly subjects the gut hyperaemia associated with food ingestion is not accompanied by concomitant increases in cardiac output and heart rate. This failure of cardiovascular adjustment to the vascular demands by the gut is likely to contribute to the fall in blood pressure seen in these healthy elderly subjects.
Altered glomerular steady-state levels of tumour necrosis factor-α mRNA during nephrotic and sclerotic phases of puromycin aminonucleoside nephrosis in rats
Authors: Nakamura Tsukasa , Ebihara Isao , Fukui Mitsumine , Takahashi Toshimasa , Tomino Yasuhiko , Koide Hikaru
Published: August 2015

1. We determined glomerular and medullary tumour necrosis factor-α mRNA levels in acute puromycin aminonucleoside nephrosis on days 0, 8 and 20.

2. Tumour necrosis factor-α mRNA levels were increased fourfold in glomeruli and twofold in the medulla during the nephrotic stage of acute puromycin aminonucleoside nephrosis (day 8).

3. The high tumour necrosis factor-α mRNA levels in both glomeruli and the medulla were ameliorated significantly by methylprednisolone administration.

4. Focal glomerular sclerosis was induced in rats by injection of puromycin aminonucleoside on days 0, 27, 34 and 41 and by unilateral nephrectomy on day 22.

5. The percentage of sclerosing glomeruli was 16.6% on day 48 and had increased significantly to 72.8% on day 80.

6. During the sclerotic phase of puromycin amino-nucleoside nephrosis, glomerular tumour necrosis factor-α mRNA levels increased as glomerular sclerosis progressed. On day 80, glomerular tumour necrosis factor-α mRNA levels were 13-fold higher than levels in control rats.

7. These data suggest that glomerular tumour necrosis factor-α mRNA expression is associated with the development of puromycin aminonucleoside-induced glomerular sclerosis.
Elevation of Serum Triacylglycerol Concentration in Association with Hepatic Microsomal Enzyme Induction after Treatment with Phenylbutazone and Diclofenac Sodium in Rats
Authors: Farag Mahmoud M. , Hassib Amel T.
Published: August 2015

1. The relationship between serum triacylglycerol concentration and hepatic microsomal enzyme activity was examined in rats.

2. Two groups of rats were injected with diclofenac sodium at doses of 2.5 and 5 mg day−1 kg−1. A third group was injected with phenylbutazone at a dose of 20 mg day−1 kg−1. The treatment was continued for 15 days and the rats were killed 24 h after the last dose.

3. In all drug-treated rats, the serum triacylglycerol concentration and the hepatic microsomal activities of aminopyrine N-demethylase and aniline hydroxylase were significantly increased as compared with the corresponding values in control rats. The correlations between the serum triacylglycerol concentrations and the activities of the two enzymes, as indices of the hepatic microsomal activity, were highly significant.

4. These results indicate that the possibility of hypertriglyceridaemia as an adverse effect of the induction of the hepatic microsomal enzymes after the administration of phenylbutazone and diclofenac sodium should be considered.
A Novel Method for Measuring Antioxidant Capacity and its Application to Monitoring the Antioxidant Status in Premature Neonates
Authors: Miller Nicholas J. , Rice-Evans Catherine , Davies Michael J. , Gopinathan Vimala , Milner Anthony
Published: August 2015

1. A new method has been developed for measuring the total antioxidant capacity of body fluids and drug solutions, based on the absorbance of the ABTS*+ radical cation.

2. An automated method for use on a centrifugal analyser, as well as a manual method, is described.

3. The procedure has been applied to physiological antioxidant compounds and radical-scavenging drugs, and an antioxidant ranking was established based on their reactivity relative to a 1.0 mmol/l Trolox standard.

4. The Trolox equivalent antioxidant capacity of plasma from an adult reference population has been measured, and the method optimized and validated.

5. The method has been applied to investigate the total plasma antioxidant capacity of neonates and how this may be compromised in prematurity.
Glucose-Dependent Uptake of Chromium in Human and Rat Insulin-Sensitive Tissues
Authors: Morris Brian W. , Gray Trevor A. , MacNeil Sheila
Published: August 2015

1. This study was designed to investigate the influence of insulin and glucose on the distribution of trivalent chromium in human plasma and blood cells and in human and rat insulin-sensitive and -insensitive tissues.

2. Evidence is provided that, in the rat in vitro, a clear difference exists in chromium binding between insulin-sensitive and -insensitive tissues in that chromium binding is significantly enhanced by glucose in insulin-sensitive tissues.

3. Glucose-dependent association of chromium with human adipose tissue was blocked by inhibitors of glucose transport.

4. Addition of insulin slightly increased the response to glucose in muscle and reduced the response to glucose in adipose tissue; such effects were less marked than those seen in response to glucose alone.

5. The results of this study in vitro support the hypothesis that, in vivo, chromium translocates from the blood compartment to insulin-sensitive tissues.
Rapid and Selective Inhibition of Platelet Aggregation and Thromboxane Formation by Intravenous Low Dose Aspirin in Man
Authors: Böger Rainer H. , Bode-Böger Stefanie M. , Gutzki Frank M. , Tsikas Dimitrios , Weskott Hans-P. , frölich Jürgen C.
Published: August 2015

1. One of the major problems in the clinical use of low dose aspirin for the prevention of vascular occlusion is that it takes about 3–5 days to become effective, a time too long for patients with unstable angina or coronary thrombolysis. Intravenous aspirin may be expected to exert a more rapid effect, but its influence on endothelial prostacyclin synthesis is uncertain.

2. In a single-blind, randomized, prospective study, we compared the effects of a single intravenous low dose (50 mg) or high dose (500 mg) of aspirin or placebo infused over a 60 min period on platelet aggregation, platelet thromboxane A2 production and whole-body prostanoid synthesis in 10 healthy male subjects by gas chromatography-tandem mass spectrometry.

3. Before the study, blood flow rates in the basilic and subclavian veins were determined by sonographic colour velocity imaging; the infusion rate for low dose aspirin was calculated to avoid biologically effective plasma levels of aspirin in the systemic circulation.

4. Platelet aggregation induced by 1 mmol/l arachidonic acid was similarly inhibited by >85% within 30 min after the start of the infusion of high dose or low dose aspirin, respectively, and remained suppressed for 24 h. Platelet thromboxane A2 release declined gradually after low dose aspirin, reaching a minimum of 93% inhibition after 60 min. High dose aspirin suppressed platelet thromboxane A2 release to below the detection limit after 10 min.

5. Urinary excretion of the major urinary metabolite of thromboxane A2 (2,3-dinor-thromboxane B2) was equally suppressed by both dosages of aspirin [no significant difference between high dose (−83.2%) and low dose (−67.4%)]. The urinary excretion of the major urinary metabolite of prostacyclin (2,3-dinor-6-keto-prostaglandin F1α) and of prostaglandin E2 was also markedly decreased, by 79.2% and 63.5%, respectively, by high dose aspirin, whereas low dose aspirin suppressed 2,3-dinor-6-keto-prostaglandin F1α excretion significantly less (−30.3%; P <0.02), and had no inhibitory effect at all on prostaglandin E2 excretion, indicating that after intravenous low dose aspirin no biologically active acetylsalicylate was present in the systemic circulation.

6. These data show that intravenous low dose aspirin can inhibit platelet aggregation and thromboxane B2 synthesis within less than 2 h while sparing systemic cyclo-oxygenase activity. Partial inhibition of prostacyclin formation seems to be an unavoidable consequence of effective inhibition of platelet cyclooxygenase by aspirin.
Effect of Insulin-Dependent Diabetes Mellitus on Lipids and Lipoproteins: A Study of Identical Twins
Authors: Dubrey Simon W. , Reaveley David A. , Leslie David G. , O'Donnell Martina , O'Connor Bernadette M. , Seed Mary
Published: August 2015

1. Forty-five identical twin pairs, discordant for insulin-dependent diabetes mellitus, were studied with respect to their serum lipid (high-density lipoprotein, low-density lipoprotein, total cholesterol and triacylglycerol) and apoprotein [apoprotein A-I, apoprotein B and lipoprotein (a)] concentrations and apoprotein (a) phenotypes. The twins were compared with an age- and sex-matched non-diabetic control group.

2. A significantly higher value was found only for high-density lipoprotein cholesterol in the diabetic twins of the female twin pairs.

3. Highly significant correlations existed between the twin pairs for all lipids and lipoproteins measured, particularly lipoprotein (a), for which identical apoprotein (a) isoforms were also found.

4. Correlations existed between the non-diabetic twins and the control subjects for high-density lipoprotein cholesterol and apoprotein A-I, probably due to the rigorous matching of control subjects.

5. The similarity between values for lipids and lipoproteins in the non-diabetic twins and control subjects suggested no effect of a genetic susceptibility to insulin-dependent diabetes mellitus. The differences in lipoproteins we describe for the identical twins discordant for insulin-dependent diabetes mellitus, in whom there was no evidence of a raised urinary albumin excretion rate, does not appear to explain the excess mortality from cardiovascular disease reported in patients with this disease.
Utilization of Non-Protein Nitrogen in Whey-Dominant Formulae by Low-Birth Weight Infants
Authors: Darling P. , Wykes L. J. , Clarke R. , Papageorgiou A. , Pencharz P. B.
Published: August 2015

1. The effects of increasing non-protein nitrogen intake on nitrogen balance and α-amino nitrogen flux rate using [15N]glycine were examined in 30 low-birthweight appropriate-for-gestational-age infants (birthweight 1.5-2.0 kg). The compositions of the three whey-dominant formulae were similar except for the ratios of non-protein nitrogen/protein nitrogen, which were 6.5:93.5, 11.4:88.6 and 17.5:82.5.

2. Infants in the three diet groups each received similar total nitrogen intakes (395 mg of N day−1 kg−1, SD 2.6; n = 3). Protein nitrogen and non-protein nitrogen intakes were different as expected. Energy absorption (449 kJ day−1 kg−1, SD 13; n = 3) did not differ significantly between groups. A similar weight gain was observed in all groups.

3. Nitrogen absorption (76%, SD 4; n = 3) was not significantly different between groups. Apparent urea balance was significantly increased and became positive in the group receiving the formula with the higher proportion of non-protein nitrogen and urea nitrogen. Nitrogen retention, however, was significantly depressed in this group, indicating decreased efficiency of nitrogen utilization at this level of non-protein nitrogen despite an enhanced urea salvage.

4. The enrichment of the 15N label in urinary urea at isotopic steady state was significantly reduced in infants receiving the highest urea-containing formula, presumably due to the dilution of 15N-labelled urea by dietary urea. No difference, however, was found in the enrichment of the 15N label in urinary ammonia. Rates of α-amino nitrogen flux, protein synthesis and protein breakdown calculated from the ammonia labelling did not differ significantly between groups.

5. The source of dietary nitrogen affects the enrichment of urinary nitrogenous end-products and must be taken into account when interpreting results of protein turnover studies using constant infusion of [15N]glycine.

6. Based on the nitrogen balance results, the nonprotein nitrogen content of formulae should not account for more than 12% of total nitrogen.
Influence of Oral Creatine Supplementation of Muscle Torque during Repeated Bouts of Maximal Voluntary Exercise in Man
Authors: Greenhaff Paul L. , Casey Anna , Short Anthony H. , Harris Roger , Soderlund Karin , Hultman Eric
Published: August 2015

1. The present experiment was undertaken to investigate the influence of oral creatine supplementation, shown previously to increase the total creatine content of human skeletal muscle (Harris RC, Soderlund K, Hultman E. Clin Sci 1992; 83: 367–74), on skeletal muscle isokinetic torque and the accumulation of plasma ammonia and blood lactate during five bouts of maximal exercise.

2. Twelve subjects undertook five bouts of 30 maximal voluntary isokinetic contractions, interspersed with 1 min recovery periods, before and after 5 days of placebo (4 × 6 g of glucose/day, n = 6) or creatine (4 × 5 g of creatine plus 1 g of glucose/day, n = 6) oral supplementation. Muscle torque production and plasma ammonia and blood lactate accumulation were measured during and after exercise on each treatment

3. No difference was seen when comparing muscle peak torque production during exercise before and after placebo ingestion. After creatine ingestion, muscle peak torque production was greater in all subjects during the final 10 contractions of exercise bout 1 (P <0.05), throughout the whole of exercise bouts 2 (P <0.01), 3 (P <0.05) and 4 (P = 0.057) and during contractions 11–20 of the final exercise bout (P <0.05), when compared with the corresponding measurements made before creatine ingestion. Plasma ammonia accumulation was lower during and after exercise after creatine ingestion. No differences were found when comparing blood lactate levels.

4. There is evidence to suggest that the decrease in the degree of muscle torque loss after dietary creatine supplementation may be a consequence of a creatine-induced acceleration of skeletal muscle phosphocreatine resynthesis. It is postulated that an increased availability of phosphocreatine would maintain better the required rate of ATP demand during contraction. This is supported by the observed lower accumulation of plasma ammonia during exercise after creatine ingestion.
Suppression of Non-Esterified Fatty Acids and Triacylglycerol in Experimental Animals by the Adenosine Analogue GR79236
Authors: Strong P. , Anderson R. , Coates J. , Elus F. , Evans B. , Gurden M.F. , Johnstone J. , Kennedy I. , Martin D.P.
Published: August 2015

1. This is the first description of the metabolic activity of a novel adenosine A1-receptor agonist, GR79236. GR79236 inhibited catecholamine-induced lipolysis in human, rat and dog isolated adipocytes.

2. Oral administration of GR79236 (0.1-10 mg/kg) to fed rats induced minimal changes in the plasma concentration of non-esterified fatty acids and in the blood concentrations of glucose and lactate.

3. Intravenous infusion of GR79236 to fasted pithed rats, or oral administration of GR79236 to fasted conscious rats and dogs, produced time- and dose-dependent decreases in the plasma non-esterified fatty acid concentration. In the fasted rats, doses of GR79236 that lowered plasma levels of non-esterified fatty acids also produced hypotriglyceridaemia and anti-ketotic effects.

4. Only in the pithed rats were acute effects on the plasma glucose and lactate concentrations observed. Hypoglycaemia and hyperlactataemia occurred over the dose range studied (1 × 10−11-1 × 10−8 mol min−1 kg−1).

5. This profile of activity suggests that compounds such as GR79236 might be agents which can be used to define the role of excessive lipolysis in experimental (and human) pathophysiology.
Renal and Hormonal Effects of Chronic Inhibition of Neutral Endopeptidase (EC 3.4.24.11) in Normal Man
Authors: O'Connell Janice E. , Jardine Alan G. , Davies David L. , McQueen James , Connell John M. C.
Published: August 2015

1. Acute pharmacological inhibition of the enzyme neutral endopeptidase (EC 3.4.24.11), which cleaves the cardiac hormone atrial natriuretic peptide, raises endogenous levels of the hormone. Short-term administration of inhibitors causes natriuresis and diuresis in normal and hypertensive subjects; we report here the effects of an orally active neutral endopeptidase inhibitor (candoxatril, 200 mg) given twice daily for 10 days to normal salt-replete male subjects (n = 12) in a placebo-controlled cross-over study.

2. Candoxatril administration caused a transient natriuresis on day 1 of treatment, but this was not sustained, and cumulative sodium excretion at the end of the study was not altered by active therapy [1720 ± 40 versus 1734 ± 57 (placebo) mmol; means ± SEM]; exchangeable body sodium content was similarly unchanged. However, urinary cyclic GMP excretion was elevated throughout the active treatment phase when compared with placebo.

3. Although a change in plasma levels of atrial natriuretic peptide could not be demonstrated, platelet atrial natriuretic peptide binding sites were reduced by active treatment [23 ± 3 versus 39 ± 4 (placebo) fmol/109; P <0.001].

4. Basal blood pressure and heart rate were not affected by candoxatril treatment. After 10 days of therapy subjects were given incremental infusions of angiotensin II (2, 4 and 8 ng min−1 kg−1) followed by phenylephrine. Although active therapy had not altered basal plasma concentrations of active renin and angiotensin II, levels of angiotensin II during infusion of the octapeptide were higher during the active phase. The diastolic pressor response to angiotensin II was increased during candoxatril treatment, although this is likely to reflect the higher plasma levels of angiotensin II during infusion of the octapeptide. In contrast, the systolic and diastolic pressor responses to phenylephrine were reduced by active treatment.

5. In conclusion, chronic candoxatril administration increases urinary cyclic GMP excretion without causing sustained natriuresis; evidence of atrial natriuretic peptide receptor down regulation was seen. There were no sustained hormonal or haemodynamic changes during therapy. The increased levels of angiotensin II during its infusion in the presence of candoxatril may reflect the role of neutral endopeptidase in clearing angiotensin II from the circulation.
Variability of Cardiovascular and Plasma Noradrenaline Responses to Sustained Isometric Contraction in Normal Human Subjects
Authors: Vaz M. , Kumar M. V. Shailesh , Kulkarni R. N. , Rodrigues D. , Shetty P. S.
Published: August 2015

1. Eight healthy adult males underwent three sustained isometric contractions at 30% of maximal voluntary contraction for 3 min, within a 9 day period.

2. The study focuses on the inter-individual and day-to-day intra-individual variability of cardiovascular and plasma noradrenaline responses to sustained isometric contraction.

3. The results of this study indicate that inter-individual variability is generally greater than intra-individual variability. Diastolic blood pressure was the most sensitive as well as the least variable cardiovascular parameter measured.

4. The variability of plasma noradrenaline levels in both the basal and the stimulated state was high. The present study suggests that it is preferable to determine the ‘true’ noradrenaline peak after the release of handgrip, as this is associated with a lower variability than the plasma noradrenaline peak taken at the time of the release of handgrip.
Lipid Metabolism after Liver Transplantation from a Living Related Donor
Authors: Sano Kaoru , Tanaka Akira , Uemoto Shinji , Honda Kazuo , Tanaka Koichi , Ozawa Kazue
Published: August 2015

1. The recovery of lipid metabolism was investigated in paediatric patients treated for terminal liver disease by liver transplantation from living related donors.

2. The cholesterol ester ratio (esterified cholesterol/total cholesterol) and the total cholesterol/phospho-lipid ratio increased from preoperative values of 0.35 ± 0.04 and 0.59 ± 0.03 to 0.65 ± 0.01 and 0.68 ± 0.01 at 3 weeks after liver transplantation in successful cases (means ± SEM, n = 26), respectively, whereas these two parameters decreased in failed cases (n = 4).

3. Biochemical analysis indicated that weekly recoveries in the cholesterol ester ratio and the total cholesterol/phospholipid ratio are characteristic of successful liver transplantation with a graft from a living related donor.
Changes in the Anterior Chamber of the Eye during Acute Hypoglycaemia in Humans
Authors: Hepburn D. A. , Clark C. V. , Pell A. C. H. , McIver B. , Frier B. M.
Published: August 2015

1. The changes in the volume and depth of the anterior chamber of the eye during acute insulin-induced hypoglycaemia were examined in nine healthy non-diabetic subjects (aged 23–31 years). The dimensions of the anterior chamber of the eye were measured by a photogrammetric technique, with Polaroid photographs taken of the lower half of the mid-sagittal plane of the eye at an angle of 55° at a magnification of × 16. Photographs were taken before and at regular intervals after the induction of acute hypoglycaemia using an infusion of unmodified (soluble) insulin at 2.5 m-units min−1 kg−1. Plasma adrenaline was measured regularly throughout the study.

2. Plasma glucose fell from 4.5 ± 0.2 mmol/l (mean ± SEM) to a nadir of 1.0 ± 0.1 mmol/l (P <0.01), which coincided with the onset of the acute autonomic reaction. Plasma adrenaline rose from 0.3 ± 0.1 nmol/l to a peak of 3.2 ± 0.6 nmol/l (P <0.01) at 15 min after the autonomic reaction.

3. The volume of the anterior chamber decreased by 8.2% from 284.7 ± 21.5 μl at baseline to 264.5 ± 17.0 μl (P <0.01) at the onset of the autonomic reaction. No significant alteration in axial anterior chamber depth was evident, but peripheral anterior depth decreased from 2.25 ± 0.20 mm at baseline to 2.07 ± 0.14 mm (P <0.05) at the onset of the autonomic response. Pupillary constriction was demonstrated in all subjects, which was most marked at 10 min after the autonomic reaction (baseline 5.0 ± 0.2 mm versus 10 min after reaction 3.7 ± 0.2 mm, P < 0.001).

4. This study has demonstrated an alteration in the dimensions and a reduction in volume of the anterior chamber of the eye in humans during acute insulin-induced hypoglycaemia. These changes in the anterior segment of the eye are probably mediated by autonomic mechanisms which are stimulated by hypoglycaemia.
Abnormalities in Skeletal Muscle Metabolism in Cyanotic Patients with Congenital Heart Disease: A 31P Nuclear Magnetic Resonance Spectroscopy Study
Authors: Adatia I. , Kemp G. J. , Taylor D. J. , Radda G. K. , Rajagopalan B. , Haworth S. G.
Published: August 2015

1. Exercise tolerance is impaired in congenital heart disease. To examine the possible contribution of abnormalities in skeletal muscle bioenergetics, we used 31P nuclear magnetic resonance spectroscopy to investigate muscle metabolism in 10 subjects with congenital heart disease with cyanosis (median age 17.3 years) and in eight healthy age-matched control subjects. Spectra were collected from the gastrocnemius muscle at rest and during exercise and recovery.

2. In resting muscle there were significant elevations in cytosolic pH and in the cytosolic concentration of inorganic phosphate in the patients, and a strong positive correlation between cytosolic pH and blood haemoglobin concentration in all subjects.

3. During plantar flexion exercise the patients showed increased phosphocreatine depletion and cytosolic acidification over a shorter duration of exercise. The rise in calculated cytosolic ADP concentration was similar in both groups.

4. After cessation of exercise, the recovery half-times of phosphocreatine, ADP and phosphate were two to three times longer in the patients, and the initial rate of phosphocreatine resynthesis (a measure of the rate of mitochondrial ATP synthesis) was half the control value, consistent with a reduction in the effective maximum rate of oxidative ATP synthesis (expressed per volume of muscle). Also, recovery was faster in the young control subjects than in our earlier studies of older healthy control subjects.

5. The high phosphate concentration in resting muscle and the abnormalities found in exercise and recovery are consistent with a decrease in oxidative ATP synthesis due to reduced oxygen delivery by the blood in chronic hypoxaemia. The correlation between cytosolic pH and haemoglobin concentration remains to be explained.
1H-Nuclear Magnetic Resonance Studies of Human Synovial Fluid in Arthritic Disease States as An Aid to Confirming Metabolic Activity in the Synovial Cavity
Authors: Duffy J. M. , Grimshaw J. , Guthrie D. J. S. , McNally G. M. , Mollan R. A. B. , Spedding P. L. , Trocha-Grimshaw J. , Walker B. , Walsh E.
Published: August 2015

1. A 1H-n.m.r. method was used to measure concentrations of valine, alanine, lactate, acetate, hyaluronan and lipids in synovial fluid obtained, during the normal course of examination, from the knee joints of patients attending rheumatology and orthopaedic clinics. Fluid was available from 16 patients with osteoarthritis, 18 patients with rheumatoid arthritis, four patients with meniscal tear and one patient each with systemic lupus erythematosis, mono-arthritis, synovitis and loose bodies. Four normal specimens were obtained for comparison.

2. Valine, alanine and acetate levels all showed a normal Gaussian distribution, reflecting the distributions within the serum of the sample population.

3. Lactate concentrations divided into two distinct patterns. At concentrations below 2.5 mmol/l the lactate levels showed a Gaussian distribution, reflecting the distribution in normal serum. The normal synovial fluid specimens belong to this distribution. Above 2.5-3.0 mmol/l, lactate levels were asymmetric in distribution with a long tail at higher concentrations. These high levels of lactate can be explained by the generation of lactate through anaerobic metabolism within the synovial cavity. This metabolic process is triggered by a general inflammatory condition such as in rheumatoid arthritis.

4. The distribution of n.m.r.-observable lipid concentrations in rheumatoid arthritis and osteoarthritis each shows a normal distribution and the mean concentration is significantly higher in rheumatoid arthritis.

5. An increased n.m.r.-observable hyaluronan concentration is associated with an inflammatory situation.

6. It is concluded that raised levels of lactate and n.m.r.-observable hyaluronan and lipids are useful markers to aid the clinical distinction between rheumatoid arthritis and osteoarthritis. The results of this study confirm rheumatoid arthritis as an inflammatory disease inducing higher metabolic activity within the synovial cavity.
Validity of Peak Expiratory Flow Rate Variability for the Diagnosis of Asthma
Authors: Jamison J. P. , McKinley R. K.
Published: August 2015

1. The aim of this study was to determine the validity of various numerical indices of peak flow variability as tests for asthma.

2. Normal (n = 24) and asthmatic (n = 123) subjects aged 10-70 years were recruited from the community. Asthma was diagnosed by full clinical assessment and was active during the previous year. Subjects recorded their peak flow immediately after rising in the morning, at 18.00 hours and just before retiring at night for 12 days.

3. The most discriminating index was the highest peak flow variability which occurred within any 1 day during the 12-day recording period, calculated as the difference between the maximum and minimum peak flows expressed as a percentage of the minimum peak flow on that day (the proposed index). This index was <20% (90th centile) in 96% of the normal subjects and ≧ 20% in 89% of the asthmatic subjects.

4. Standard indices of mean peak flow, the forced expiratory volume in 1.0 s and its responsiveness to salbutamol, had much lower sensitivities than peak flow variability.

5. It is concluded that numerical indices of peak flow variability are highly valid tests for asthma. Using an upper limit of normal of 20%, the proposed index of peak flow variability discriminates better than other indices between asthmatic and normal subjects.
Effects of Angiotensin II on Insulin Sensitivity: A Placebo-Controlled Study
Authors: Morris A. D. , Petrie J. R. , Anderson J. , Connell J. M. C. , Donnelly R.
Published: August 2015

1. There is evidence that hyperinsulinaemia increases the aldosterone response to angiotensin II, and that angiotensin-converting enzyme inhibitor drugs enhance peripheral glucose utilization, but the direct effects of angiotensin II on insulin sensitivity have not been reported previously.

2. In a randomized, double-blind, placebo-controlled, cross-over study, 12 healthy male subjects attended on 3 study days for the evaluation of the effects of a subpressor (1 ng min−1 kg−1) and pressor (5 ng min−1 kg−1) infusion of angiotensin II on whole-body insulin sensitivity using the euglycaemic hyperinsulin-aemic clamp. Frequent measurements of blood pressure and heart rate were recorded and blood samples were collected for determination of serum insulin, C-peptide and K+ concentration, plasma renin activity and plasma angiotensin II concentration.

3. Plasma angiotensin II concentrations (means +SD) were 11+5 pg/ml after placebo, and 27+9 and 125+28 pg/ml after low and high dose angiotensin II, respectively. The higher dose of angiotensin II was associated with significant increases in blood pressure (e.g. 13 mmHg systolic blood pressure at 150 min) and serum aldosterone concentration. Whole-body insulin sensitivity was 10.5 + 2 mg of glucose min−1 kg−1 after placebo, and 10.5 +2.2 and 10.9+3.4 mg of glucose min−1 kg−1 after low and high dose angiotensin II (not significant).

4. Angiotensin II had no effect on hyperinsulinaemia-induced reductions in serum potassium and triacyl-glycerol concentrations.

5. Thus, acute infusion of angiotensin II for 3 h, with or without an increase in blood pressure, has no effect on whole-body insulin sensitivity.
Determination of Free Polyamines in Human Bile by High-Performance Liquid Chromatography
Authors: Hallak A. , Rosenberg R. , Gilat T. , Sömjen G. J.
Published: August 2015

1. Polyamines are widely distributed in the body and may have cholesterol-nucleating activity in model bile and human bile. There are only partial and scant data available on the type of polyamines in human bile.

2. In this study methods for extraction of free polyamines, benzoylation and an h.p.l.c.-based method for the quantitative determination of putrescine, cadaverine, spermidine and spermine in bile are described. The h.p.l.c. methodology was validated and compared with separation on t.l.c. after dansylation.

3. The polyamine content of 11 gallbladder bile samples and 11 T-tube bile samples was analysed, all from patients with gallstones. Polyamines were found in three out of 11 gallbladder bile samples and eight out of 11 T-tube bile samples. Putrescine levels were 0.5-287 μmol/l and cadaverine levels were 2.4-645.4 μmol/l; these were considerably higher than spermine and spermidine levels.

4. As many of these gallstones bile samples were devoid of polyamines, it is questionable whether polyamines play an important role in cholesterol nucleation in human bile.
Extracellular Volume Expansion Inhibits Antidiuretic Hormone Increase during Positive End-Expiratory Pressure in Conscious Dogs
Authors: Kaczmarczyk Gabriele , Jörres Dinah , Rossaint Rolf , Krebs Martin , Unger Volker , Falke Konrad
Published: August 2015

1. This study in conscious dogs examined the effects of extracellular volume expansion on plasma antidiuretic hormone, atrial natriuretic peptide and aldosterone concentrations, plasma renin activity, and haemodynamic and renal responses during controlled mechanical ventilation with 20 cmH2O positive end-expiratory pressure.

2. Twenty experiments (10 controls, 10 expansion experiments with 03 ml min−1 kg−1 body weight of a balanced electrolyte solution given intravenously throughout) were performed in five trained, conscious, tracheotomized dogs over 4 h: first and fourth hour, spontaneous breathing; second and third hour, 20 cmH2O positive end-expiratory pressure.

3. In the control experiments positive end-expiratory pressure increased plasma antidiuretic hormone concentration from 1.4 + 0.2 to 10.0 + 3.3 pg/ml, plasma aldosterone concentration from 113 + 19 to 258 + 58 pg/ml and heart rate from 77 + 5 to 94 + 5 beats/min. Positive end-expiratory pressure did not change plasma atrial natriuretic peptide concentration (55 + 5 pg/ml), plasma renin activity (2.6 + 0.4 pmol of angiotensin I h−1 ml−1) and mean arterial pressure 103 + 3 mmHg).

4. In the expansion experiments, positive end-expiratory pressure did not change plasma antidiuretic hormone concentration (1.1 + 0.1 pg/ml), plasma aldosterone concentration (25 + 2 pg/ml), plasma atrial natriuretic peptide concentration (82 + 8 pg/ml), plasma renin activity (0.8 + 0.15 pmol of angiotensin I h−1 ml−1), heart rate (92 + 6 beats/min) and mean arterial pressure (111 + 4 mmHg).

5. In the control experiments, urine volume, sodium excretion and fractional sodium excretion remained in a low range during positive end-expiratory pressure, whereas potassium excretion increased. In the expansion experiments, urine volume, sodium excretion and fractional sodium excretion increased continuously. Glomerular filtration rate was decreased during positive end-expiratory pressure in the control experiments when compared with the expansion experiments (3.4 + 0.3 versus 3.9 + 0.2 ml min−1 kg−1 body weight).

6. Arterial blood gases and plasma osmolality did not change in either protocol.

7. It is suggested that the striking increase in antidiuretic hormone may play a part in the circulatory control mechanisms that maintain mean arterial pressure during positive end-expiratory pressure when the extracellular volume is not expanded.
Inhibition of Nitric Oxide Synthesis in Forearm Vasculature of Insulin-Dependent Diabetic Patients: Blunted Vasoconstriction in Patients with Microalbuminuria
Authors: Elliott T. G. , Cockcroft J. R. , Groop P.-H. , Viberti G. C. , Ritter J. M.
Published: August 2015

1. Microalbuminuria is a risk factor for cardiovascular disease in patients with insulin-dependent diabetes mellitus, and may be a marker of microvascular dysfunction including endothelial damage. The purpose of this study was to determine whether vasoconstrictor responses to NG-monomethyl-L-arginine, an inhibitor of endothelium-derived relaxing factor/nitric oxide biosynthesis, differ between healthy subjects and insulin-dependent patients with or without microalbuminuria.

2. Twenty-eight insulin-dependent diabetic patients (14 with normal albumin excretion, 14 with microalbuminuria) were studied under euglycaemic conditions, together with 14 healthy control subjects. Forearm vascular responses to brachial artery infusions of NG-monomethyl-L-arginine, sodium nitroprusside (an endothelium-independent nitrovasodilator) and carbachol (an endothelium-dependent vasodilator) were determined by strain gauge plethysmography.

3. Basal blood flow and vasodilator responses were similar in each group. NG-Monomethyl-L-arginine reduced blood flow by 41.3 + 2.3% (mean + SEM) in healthy control subjects, 34.0 + 3.4% in diabetic patients without microalbuminuria and 29.2 + 2.0% in diabetic patients with microalbuminuria. Diabetic patients differed from healthy subjects (P = 0.005), due to a difference between control subjects and microalbuminuric diabetic patients (P <0.001). NG-Monomethyl-L-arginine did not influence nitroprusside responses but reduced carbachol responses in control subjects and normoalbuminuric diabetic patients but not in microalbuminuric diabetic patients.

4. These results provide evidence of abnormal endothelium-derived relaxing factor/nitric oxide biosynthesis in insulin-dependent diabetic patients with microalbuminuria.
Hydrogen Peroxide Generation in a Model Paediatric Parenteral Amino Acid Solution
Authors: Brawley Vince , Bhatia Jatinder , Karp Warren B.
Published: August 2015

1. Parenteral amino acid solutions undergo photo-oxidation, which may be an important factor in total parenteral nutrition-associated hepatic dysfunction. Light-exposed parenteral solutions containing amino acids, in addition to vitamins and trace minerals, generate free radicals, which, in turn, may contribute to this type of injury. This study examined the characteristics of H2O2 production in a parenteral amino acid solution modelled on a commercially available paediatric parenteral amino acid solution.

2. The solution was exposed to light in the presence of riboflavin-5′-monophosphate (riboflavin), and peroxide formation in the presence and absence of catalase (H2O2 formation) was assayed using potassium iodide/molybdate.

3. Peak H2O2 production occurred at a light intensity of 8 μW cm−2 nm−1 in the 425–475 nm waveband and was linear to 2 h of light exposure. H2O2 production reached 500 μmol/l at 24 h.

4. H2O2 was directly related to a riboflavin concentration of up to 20 μmol/l and was maximal at 30 μmol/l.

5. H2O2 production was greatest in the amino acid/riboflavin solution at a pH of between 5 and 6.

6. Under the conditions of light exposure intensity, light exposure time, riboflavin concentration and pH found during the administration of parenteral nutrition in neonatal intensive care units, net H2O2 production occurs in solutions modelled on a paediatric parenteral amino acid preparation.
Renal Uric Acid Handling in Non-Insulin-Dependent Diabetic Patients with Elevated Glomerular Filtration Rates
Authors: Golik A. , Weissgarten J. , Cotariu D. , Cohen N. , Zaidenstein R. , Ramot Y. , Averbukh Z. , Modai D.
Published: August 2015

1. Hypouricaemia is prevalent in diabetic patients. In most of the studies, the diabetic patients had some degree of diabetic nephropathy as evidenced by a decreased glomerular filtration rate and proteinuria. Therefore we studied renal uric acid handling in a group of type II diabetic patients with elevated glomerular filtration rates.

2. Eighteen type II diabetic patients with normal kidney functions and elevated glomerular filtration rate and a group of 18 healthy, age- and weight-matched control subjects, were studied. Serum fructosamine, creatinine and uric acid levels were determined. Twenty-four hour urine collections were obtained, and microalbumin, glucose, creatinine and uric acid, were measured.

3. The creatinine clearance was higher and the serum uric acid concentration was lower in the diabetic patients (P <0.05). The 24 h urinary uric acid excretion and filtered uric acid load were similar in both groups. However, the derived parameters of uric acid clearance and fractional excretion were significantly higher in the diabetic patients (P <0.002 and P <0.05, respectively). A negative correlation was apparent between serum fructosamine concentration and serum uric acid concentration (r = −0.76). A positive correlation was found between serum fructosamine concentration and fractional uric acid excretion (r = 0.64) and between serum fructosamine concentration and filtered uric acid load (r = 0.66). A positive correlation was found between creatinine clearance and 24 h uric acid excretion (r = 0.61) and between creatinine clearance and filtered uric acid load (r = 0.82).

4. It appears that the hypouricaemia and hyperuricosuria in diabetic patients are associated with an elevated glomerular filtration rate and a net tubular reabsorptive defect that may herald the development of diabetic nephropathy.