bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Residual Insulin Secretion (Assessed by C-Peptide Concentration) Affect Lipid and Lipoprotein Levels in Insulin-Dependent Diabetes Mellitus?
Authors: Winocour Peter H. , Durrington Paul N. , Ishola Monica , Gordon Chris , Jeacock Julie , Anderson David C.
Published: August 2015

1. Residual endogenous insulin secretion can be assessed by the circulating C-peptide concentration and is present in up to 15% of subjects with established insulin-dependent diabetes mellitus (IDDM). Its role in lipid metabolism in IDDM is not clearly defined. We examined the relationships between serum lipid and lipoprotein concentrations and the response of circulating C-peptide to a test meal in 205 subjects with IDDM.

2. Lipid and lipoprotein levels and glycaemic control did not differ significantly between patients with undetectable, low or high C-peptide responses.

3. High density lipoprotein (HDL) cholesterol and its subfractions were inversely related to concentrations of serum triacylglycerols (P < 0.01–0.001), but not to C-peptide or glycated haemoglobin (HbA,) levels. Levels of HbA, and triacylglycerols were correlated with one another (P < 0.01). Analysis of variance revealed that differences in gender and triacylglycerol concentrations were the most important determinants of HDL and HDL2 cholesterol levels. C-peptide only exerted a weak effect on HDL2 cholesterol levels and no significant predictors of HDL3 cholesterol were found.

4. It is concluded that endogenous insulin secretion (assessed by C-peptide concentration) is relatively unimportant in modifying HDL metabolism in IDDM and that associated clinical features, in particular ambient hypertriglyceridaemia, are of greater importance.
Human Forearm Arteriovenous Differences of Carnitine, Short-Chain Acylcarnitine and Long-Chain Acylcarnitine
Authors: Bartlett Dr K. , Bhuiyan A. K. M. J. , Aynsley-Green A. , Butler P. C. , Alberti K. G. M. M.
Published: August 2015

1. Forearm arterial and venous concentrations of free carnitine, short-chain acylcarnitine, long-chain acylcarnitine, glucose, lactate, pyruvate, alanine, non-esterified fatty acids, glycerol, 3-hydroxybutyrate and acetoacetate were measured in fasted adult subjects.

2. In all subjects there was net uptake of short-chain acylcarnitine, 3-hydroxybutyrate and acetoacetate and net release of free carnitine and non-esterified fatty acids. The arteriovenous differences of the other metabolites were not consistent.

3. These observations support the concept that short-chain acylcarnitine (largely acetylcarnitine) contributes to the flux of metabolic fuels from the liver to muscle in the fasted state, although to a limited extent in comparison with 3-hydroxybutyrate (< 5% on a molar basis).
Effect of Ligustrazine on Pulmonary Vascular Changes Induced by Chronic Hypoxia in Rats
Authors: Cai Y. N. , Barer G. R.
Published: August 2015

1. Acute and chronic effects on the pulmonary circulation of ligustrazine, a chemically identified and synthesized principle of a Chinese herb, were studied in rats. It dilated lung vessels and reversed hypoxic pulmonary vasoconstriction.

2. In rats kept 2 weeks in 10% O2 in a normobaric chamber and simultaneously treated with ligustrazine, right ventricular hypertrophy and muscularization of pulmonary arterioles were attenuated compared with saline-treated rats. Pulmonary artery pressure, measured in isolated lungs perfused at a constant flow rate, was also less in ligustrazine-treated rats.

3. In isolated blood-perfused lungs of chronically hypoxic and control rats, the relation between pressure and flow was measured during normoxia (ventilation with air plus 5% CO2), hypoxia (2% O2 plus 5% CO2) and after ligustrazine during continued hypoxia. Alveolar pressure was always greater than left atrial pressure; thus flow was determined by the pulmonary artery minus alveolar pressure difference.

4. Pressure/flow lines were measured during normoxia in four groups of rats: (1) control, saline-treated; (2) control, ligustrazine-treated; (3) chronically hypoxic, saline-treated; (4) chronically hypoxic, ligustrazine-treated. Both chronically hypoxic groups had steeper lines (higher resistance) than the control groups, which were similar in all respects. However, in chronically hypoxic rats, the extrapolated intercept of the line on the pressure axis, probably attributable to small newly muscularized arterioles in a state of tore, was much increased in the saline-treated group but did not differ from controls in the ligustrazine-treated group.

5. The proportion of muscularized small vessels in the four groups was: control, saline-treated 6.3 ± 1.0%, control, ligustrazine-treated 5.7 ± 0.6% (not significant), chronically hypoxic, saline-treated 27 ± 3.1%, chronically hypoxic, ligustrazine-treated 14.7 ± 2.1% (P < 0.01). We attribute the change in the pressure/flow line in ligustrazine-treated hypoxic rats to this attenuation of new muscle growth.

6. After chronic ligustrazine treatment, its acute effect was undiminished.
Haemodynamic and Cerebrovascular Responses to Glycerol Infusion in Dogs
Authors: Chen Jiann-Liang , Wang Yeou-Chih , Wang Jia-Yi
Published: August 2015

1. The response of cerebral blood vessels to hyperosmolar agents in vivo remains controversial, and little is known about the effect of glycerol on cerebral vessels. In this study we investigated the cerebrovascular response to intravenous administration of glycerol (1 g/kg, infused over 25 min) in dogs under pentobarbital anaesthesia.

2. Intracranial pressure, systemic arterial pressure, mean arterial blood pressure, serum osmolarity and packed cell volume were continuously monitored, and blood gases were checked frequently. Through a parietal cranial window, pial vessel diameter was measured by means of a surgical microscope and a video image-analyser.

3. Pial vessel diameter increased gradually with a maximum at 30 min after the beginning of glycerol infusion. The maximum increase in diameter in small (< 100 μm) vessels was 14.3%, whereas that in large (> 100 μm) vessels was 10.3%. There was only a slight increase (< 4%) in pial vessel diameter in vehicle-infused animals. The intracranial pressure decreased drastically after glycerol infusion, whereas the mean arterial blood pressure remained constant. There were correlations between the rise in serum osmolarity, fall in packed cell volume and vasodilatation, indicating that glycerol caused vasodilatation accompanied by plasma volume expansion.

4. Our data suggest that glycerol produces cerebral vasodilatation, which might be beneficial in cerebral ischaemia and vasospasm, in addition to its intracranial pressure-reducing effect on normal or oedematous brain. The degree of vasodilatation was not sufficient to affect the predominant intracranial pressure drop resulting from cerebral dehydration.
Vasopressin Secretion in Diabetic Subjects with and without Autonomic Neuropathy: Responses to Osmotic and Postural Stimulation
Authors: Reid W. , Ewing D. J. , Lightman S. L. , Eadington D. , Williams T. D. M. , Roulston J. E. , Clarke B. F.
Published: August 2015

1. The release of arginine vasopressin (AVP) after an osmotic stimulus and head-up tilt was assessed in diabetic subjects with and without autonomic neuropathy

2. Six diabetic subjects with (DAN +ve) and five without (DAN − ve) evidence of autonomic neuropathy and five normal subjects were infused with 5% (w/v) NaCl at a rate of 0.05 ml min−1 kg−1 body weight for 120 min. Blood pressure, heart rate and plasma AVP were measured over this period

3. Seven DAN +ve, six DAN −ve and six normal subjects were tilted head-up to 45° for 120 min. Blood pressure, heart rate and plasma AVP were measured during the study

4. Infusion of 5% (w/v) NaCl produced appropriate rises in plasma osmolality and plasma AVP levels which did not differ between the three groups, confirming the normal osmotic release of AVP in the diabetic subjects

5. During head-up tilt, there were no differences in AVP responses between the three groups, despite a major hypotensive stimulus in the DAN + ve group

6. We conclude that osmotic release of AVP is normal in diabetes, but that cardiovascular release of AVP is impaired in diabetic subjects with cardiovascular reflex evidence of autonomic neuropathy, reflecting an afferent defect.
Effects of Insulin on Human Adipose Tissue Metabolism in Vivo
Authors: Coppack S. W. , Frayn K. N. , Humphreys S. M. , Dhar H. , Hockaday T. D. R.
Published: August 2015

1. The metabolic effects of insulin on human adipose tissue were studied by combining the euglycaemic clamp technique with measurement of arteriovenous differences across the subcutaneous adipose tissue of the anterior abdominal wall

2. Eight normal subjects were studied after an overnight fast, and for 120 min during infusion of insulin (mean arterialized plasma insulin 50–55 m-units/l)

3. During the insulin infusion, the arterialized and abdominal venous levels of both non-esterified fatty acids and glycerol fell, and the arteriovenous differences for the release of these substances narrowed. The fractional rate of re-esterification of fatty acids was around 20% in the fasting state and increased to almost 100% during hyper-insulinaemia

4. In the fasting state the uptake of glucose and 3-hydroxybutyrate by adipose tissue could account for only 20% of the oxygen uptake. During insulin infusion, adipose tissue glucose uptake increased and could account for more than 100% of oxygen uptake, implying storage of glucose

5. Net balances of different substrates across adipose tissue were examined by calculating fluxes in terms of μg-atoms of carbon. In the fasting state adipose tissue was in marked negative carbon balance (because of the export of non-esterified fatty acids); during insulin infusion it just reached ‘carbon balance’. These results were in contrast to those from a previous study of glucose ingestion, in which the adipose tissue showed marked positive carbon balance (net substrate deposition).
Ventilatory effects of hypoxia and adenosine infusion in patients after bilateral carotid endarterectomy
Authors: Griffiths T. L. , Warren S. J. , Chant A. D. B. , Holgate S. T.
Published: August 2015

1. We have studied the carotid body contribution to hypoxic respiratory drive, using a hypoxic/hyperoxic switching technique, and the ventilatory response to intravenous infusion of adenosine, a recently described respiratory stimulant, in five patients with bilateral carotid endarterectomy.

2. The contribution made by the carotid bodies to total ventilatory drive during hypoxia varied from 2.5% to 45.9%.

3. The ventilatory response to adenosine infusion varied from a 7% decrease to a 25% increase in ventilation.

4. Those patients with intact hypoxic ventilatory drive showed respiratory stimulation, whereas of the two patients with attenuated chemoreflexes, one showed no stimulation and the other depression of ventilation in response to adenosine infusion.

5. We conclude that adenosine exerts its respiratory stimulant effect via an action on the peripheral chemoreceptors. This may coexist with a centrally mediated respiratory depression that is masked when the carotid bodies are intact.
Effect of atrial natriuretic peptide on blood pressure, guanosine 3′:5′-cyclic monophosphate release and blood volume in uraemic patients
Authors: Jespersen B. , Eiskær H. , Pedersen E. B.
Published: August 2015

1. Eleven patients on chronic maintenance dialysis were investigated before and after intravenous bolus injection of atrial natriuretic peptide (2 μg/kg body weight).

2. Mean blood pressure was reduced to the same extent in the uraemic patients as in 11 healthy subjects, with a nadir 3 min after the atrial natriuretic peptide injection at which time mean blood pressure was reduced by 13% (median) in the uraemic patients and 11% in the healthy subjects.

3. Basal plasma atrial natriuretic peptide and guanosine 3′:5′-cyclic monophosphate levels were higher in the uraemic patients than in the healthy subjects, but guanosine 3′:5′-cyclic monophosphate increased markedly in both groups after atrial natriuretic peptide injection.

4. Using changes in γ-emission from blood after previous labelling of erythrocytes with 51Cr, and changes in packed cell volume, haemoglobin and erythrocyte count, a reversible shift of fluid from the intravascular phase was demonstrated in the uraemic subjects. The blood volume was maximally reduced by 6% (median) of initial blood volume at 30 min after atrial natriuretic peptide injection.

5. Correlation analyses gave no evidence of a causal relationship between the changes in mean blood pressure and changes in blood volume, angiotensin II, aldosterone or arginine vasopressin after atrial natriuretic peptide injection.

6. It is concluded that a pharmacological dose of atrial natriuretic peptide reduces blood pressure in uraemic patients on maintenance dialysis to the same extent as in healthy subjects. The blood-pressure-reducing effect of atrial natriuretic peptide does not seem to be mediated by its diuretic effect or ability to displace fluid from plasma to the interstitial fluid compartment.
A cross-sectional study of basal platelet intracellular free calcium concentration in normotensive and hypertensive primigravid pregnancies
Authors: Kilby M. D. , Pipkin F. Broughton , Cockbill S. , Heptinstall S. , Symonds E. M.
Published: August 2015

1. The intracellular free calcium concentration ([Ca2+]i) in washed human platelets was measured using the fluorescent indicator, fura-2, in a cross-sectional study of 36 normotensive, primigravid volunteers, 12 in each trimester of pregnancy and a further 12 at 6 weeks post partum. The results were compared with those obtained from 30 normal female volunteers not using oral contraception.

2. The mean basal [Ca2+]i in the platelets of the pregnant women in the first two trimesters (115.6 ± 6.7 and 120.1 ± 5.7 nmol/l, respectively) was not shown to differ significantly from that of normal non-pregnant volunteers (112.3 ± 2.9 nmol/l). However, during the third trimester a significant increase in [Ca2+]i was noted (134.0 ± 4.9 nmol/l; P < 0.05), with a return to normal values in the post-partum period (108.2 ± 6.1 nmol/l).

3. [Ca2+]i was also measured in the platelets of a group of 12 primigravid pregnant women in the third trimester whose pregnancies were complicated by gestational hypertension (pregnancy-induced hypertension and preeclampsia). A significant rise in basal [Ca2+]i was noted in the platelets of primigravidae whose pregnancies were complicated by pre-eclampsia (163.6 ± 8.8 nmol/l) as compared with normotensive, third-trimester primigravidae (P < 0.02). However, no correlation could be demonstrated between [Ca2+]i and systemic blood pressure.
Arginine vasopressin release from human platelets after irreversible aggregation
Authors: Anfossi Giovanni , Mularoni Elena , Trovati Mariella , Massucco Paola , Mattiello Luigi , Emanuelli Giorgio
Published: August 2015

1. The release of arginine vasopressin from human platelets was investigated in platelet-rich plasma after irreversible aggregation induced by adenosine 5′-pyrophosphate, collagen, sodium arachidonate, thrombin and adrenaline in vitro.

2. Arginine vasopressin levels were significantly higher in the supernatant from stimulated platelet-rich plasma than from unstimulated samples, reaching 3.5 × 10−12 (range 1.6–12.5 × 10−12) mol/l in the absence of an aggregating agent, 8.8 × 10−12 (range 4.2–17.5 × 10−12) mol/l after adenosine 5′-pyrophosphate, 13.7 × 10−12 (2.2–63.2 × 10−12) mol/l after collagen, 7.8 × 10−12 (2.2–14.6 × 10−12) mol/l after sodium arachidonate, 7.8 × 10−12 (2.2–16.3 × 10−12) mol/l after thrombin and 12.2 × 10−12 (4.8–32.1 × 10−12) mol/l after adrenaline.

3. An arginine vasopressin level of 18 × 10−12 mol/l, which can be achieved physiologically, increased the sensitivity of platelets to adenosine 5′-pyrophosphate and collagen in vitro; the same concentration of arginine vasopressin caused a potentiation of the effect of catecholamines on the response of platelets to sodium arachidonate.

4. These results indicate that intraplatelet arginine vasopressin is released during aggregation and suggest that a local release of arginine vasopressin could occur after complete platelet aggregation in vivo.
Actions of bufalin and cinobufotalin, two bufadienolides respectively more active and less active than ouabain, on ouabain binding and 86Rb uptake by human erythrocytes
Authors: Brownlee A. A. , Johnson Paul , Mills Ivor H.
Published: August 2015

1. We have reported that the bufadienolide, bufalin (purified from toad skin), was more potent than ouabain in inhibiting the sodium/potassium-dependent adenosine triphosphatase from canine kidney (Sigma) [Brownlee, A. A., Lee, G. & Mills, I. H. J. Physiol. (London) 1987; 390, 94P].

2. The activities of bufalin and cinobufotalin were compared with ouabain in the [3H]ouabain binding assay and on 86Rb uptake in human erythrocytes.

3. When the percentage binding of ouabain-sensitive [3H]ouabain was plotted against the log of the concentration of drug in mol/l, it was shown that the bufalin curve was shifted to the left of that of ouabain and that of cinobufotalin was to the right

4. Linear regression lines were fitted to the data transformed as the log of (p/1–p) plotted against the log of the drug concentration, where p is the proportion of maximal ouabain-sensitive activity at the drug concentration being considered. The IC50 (the concentration of drug producing a 50% change in the maximal ouabain-sensitive response) was 1.4 × 10−9 mol/l for bufalin, 9.7 × 10−9 mol/l for ouabain and 1.70 × 10−7 mol/l for cinobufotalin.

5. The introduction of bufalin 1 h before ouabain reduced the binding of [3H]ouabain to 23.4 ± 1.5% (P < 0.001). Bufalin added in the second hour reduced the ouabain-sensitive binding from 100 ± 1.9% to 87.4 ± 2.9% (P < 0.01).

6. The oubain-sensitive 86Rb uptake curves showed that that of bufalin was to the left of ouabain and that of cinobufotalin was to the right.

7. Regression lines were fitted to the 86Rb uptake data as described for the ouabain-binding data. The IC50 was 1.05 × 10−8 mol/l for bufalin, 4.4 × 10−8 mol/l for ouabain and 4.3 × 10−7 mol/l for cinobufotalin.

8. The differences in potencies are not all explained by what is known of the effects of structure on the cardiac toxicity of cardenolides and bufadienolides.
Effects of haemorrhage and volume expansion on portal–systemic collateral vascular resistance in conscious portal hypertensive rats
Authors: Koshy Abraham , Sekiyama Tatsuya , Cereda Jean-Michel , Hadengue Antoine , Girod Catherine , Lebrec Didier
Published: August 2015

1. In order to study the acute effects of blood volume changes on the vascular resistance of portal-systemic collaterals (collateral vascular resistance), a model of total portal vein occlusion with 100% portal-systemic shunts was developed in the rat. In this model, we determined the haemodynamic effects of haemorrhage (1.8 ml/100 g body weight) or intravenous infusion of a volume expander (1.8 ml/100 g body weight). Cardiac output and regional blood flows were measured by the radioactive microsphere method.

2. Haemorrhage significantly reduced arterial pressure from 108 ± 4 to 92 ± 4 mmHg (mean ± sem), cardiac output from 56 ± 4 to 24 ± 2 ml min−1 100 g−1 body weight, portal pressure from 15.1 ± 1.5 to 10.0 ± 1.4 mmHg and portal tributary blood flow from 19.9 ± 2.3 to 8.3 ± 1.4 ml/min. Consequently, collateral vascular resistance significantly increased from 6.6 ± 0.9 × 103 to 11.1 ± 2.0 × 103 kPal−1 s.

3. Volume expansion reduced arterial pressure from 98 ± 3 to 90 ± 3 mmHg, and significantly increased cardiac output from 43 ± 3 to 55 ± 3 ml min−1 100 g−1 body weight, portal pressure from 13.9 ± 0.7 to 16.5 ± 0.8 mmHg and portal tributary blood flow from 16.4 ± 1.3 to 28.2 ± 3.2 ml/min. Consequently, collateral vascular resistance significantly decreased from 7.0 ± 0. 5 × 103 to 4.9 ± 0.4 × 103 kPa l−1 s.

4. This study shows that in rats with portal hypertension, portal-systemic collateral vascular resistance is modified by alterations in blood volume.
A comparison of the acute effects of subcutaneous and intranasal calcitonin
Authors: O'Doherty D. P. , Bickerstaff D. R. , McCloskey E. V. , Atkins R. , Hamdy N. A. T. , Kanis A.
Published: August 2015

1. We studied the acute effects of intranasal and subcutaneous calcitonin in 40 patients with active Paget's disease of bone. Patients received a single dose of either 400 units of calcitonin delivered as a nasal spray, or 1, 10 or 100 units of subcutaneous calcitonin, or placebo.

2. Subcutaneous salmon calcitonin, administered at doses of 1, 10 and 100 units to nine patients with Paget's disease of bone, induced a dose-dependent fall in the serum calcium. This calcium-lowering effect was not seen with a second group of nine patients receiving placebo.

3. The lower doses of calcitonin had significant effects, and these were more pronounced in patients with lower rates of bone turnover.

4. Four hundred units of calcitonin administered as a nasal spray induced effects qualitatively similar to those seen with subcutaneous calcitonin, with an efficacy equivalent to approximately 30 units of subcutaneous calcitonin.

5. We conclude that the bioequivalence of calcitonin given by intranasal insufflation is low compared with its parenteral administration. The intranasal route may be more appropriate for managing patients with disorders associated with low bone turnover.
Alterations in Na+, K+ and Ca2+ transport in erythrocytes of patients with carcinomas of the head and neck: possible role of mild anaemia and cell age
Authors: Engelmann Bernd , Grevers Gerhard , Janka Hans Uwe , Duhm Jochen
Published: August 2015

1. Rates of erythrocyte Ca2+ inward transport, activities of erythrocyte Ca2+-adenosine triphosphatase, Na+, K+ pump, Na+-K+ co-transport and Na+-Li+ exchange, and erythrocyte Ca2+, K+ and Na+ contents have been determined in patients with carcinomas of the head and neck.

2. Decreases in Ca2+ inward transport and Na+-K+ co-transport activity, and increases in erythrocyte Ca2+ and K+ contents, were observed.

3. The more pronounced changes found in advanced carcinoma stages proved to be related to a 50% incidence of a mild anaemia of chronic disease in patients with carcinoma stages T3 and T4.

4. ‘Young’ (light) erythrocytes from healthy donors obtained by density centrifugation showed modifications in Na+ transport and K+ content similar to those seen in the patients.

5. It is concluded that the decrease in Na+-K+ co-transport activity, as well as the elevated K+ content and the lowered mean corpuscular haemoglobin content, but not the disturbances in Ca2+ homoeostasis, in erythrocytes of patients with carcinomas of the head and neck are most probably due to the occurrence of a mild anaemia of chronic disease in advanced carcinoma stages, associated with a reduction in mean erythrocyte age.
Atrial natriuretic factor and changes in dietary sodium intake in patients with chronic renal failure
Authors: Dussaule J. C. , Michel C. , Wolf J. P. , Czekalski S. , Mignon F. , Ardaillou R.
Published: August 2015

1. In order to examine the potential role of atrial natriuretic factor in modulating the increased sodium excretion per nephron in chronic renal failure, we studied 12 uraemic patients on the last day of two successive 7 day periods during which their sodium intake was 100 and 20 mmol of sodium/day, respectively.

2. There was a parallel decrease from 6.31 ± 0.75 to 2.17 ± 0.32% in the fractional excretion of filtered sodium and from 234.4 ± 74.9 to 80.6 ± 20.3 pg/ml (supine position) or 140.1 ± 43.6 to 60.7 ± 14.6 pg/ml (upright position) in plasma atrial natriuretic factor. Both parameters were significantly correlated during the two periods of different sodium intake (P <0.05). The ratio of plasma guanosine 3′:5′-cyclic monophosphate to plasma creatinine changed proportionally to plasma atrial natriuretic factor. Plasma aldosterone and plasma renin activity increased during the sodium-depleted period but only plasma renin activity was significantly correlated with fractional excretion of filtered sodium.

3. The predominant role of atrial natriuretic factor compared with that of aldosterone in the renal response to varying sodium intake is suggested both by regression analysis and by the effect of 5 day's treatment with a converting enzyme inhibitor (enalapril) in six other uraemic patients on a normal (100 mmol/day) sodium intake. Such treatment, although resulting in a significant increase in plasma renin activity and a significant decrease in plasma aldosterone, at least in the supine position, did not modify the fractional excretion of sodium and plasma atrial natriuretic factor.

4. Taken together, these results suggest a role for plasma atrial natriuretic factor in promoting the adaptation of sodium excretion on chronic changes of sodium intake in patients with chronic renal failure.
Peptide histidine valine: Its haemodynamic actions and pharmacokinetics in man differ from those of vasoactive intestinal peptide and peptide histidine methionine
Authors: Gill J. S. , Yiangou Y. , Webb D. J. , Meleagros L. , Benjamin N. , Chrysanthou B. J. , Cockcroft J. R. , Causon R. C. , Camm A. J. , Bloom S. R.
Published: August 2015

1. The effects of intravenous and intra-arterial infusion of the peptides derived from prepro-vasoactive intestinal peptide, vasoactive intestinal peptide, peptide histidine methionine and peptide histidine valine, were examined in six healthy volunteers.

2. Vasoactive intestinal peptide given intravenously caused a significant increase in heart rate and a decrease in diastolic, but not systolic, blood presure, whereas peptide histidine valine caused an increase in heart rate alone, despite higher achieved circulating peptide concentrations. Peptide histidine methionine did not affect heart rate or blood pressure. Forearm blood flow was increased by vasoactive intestinal peptide and peptide histidine valine when infused locally intra-arterially, although vasoactive intestinal peptide was more potent than peptide histidine valine.

3. Plasma concentrations of cardiodilatin (the N-terminal peptide derived from pro-atrial natriuretic peptide) were increased by intravenous infusion of vasoactive intestinal peptide, but were unaffected by peptide histidine methionine or peptide histidine valine. Circulating plasma concentrations of adrenaline and noradrenaline did not change during infusion of vasoactive intestinal peptide, peptide histidine methionine or peptide histidine valine.

4. Peptide histidine valine had a long half-life when compared with peptide histidine methionine and vasoactive intestinal peptide.

5. We conclude that peptide histidine valine is active in the human cardiovascular system and has a similar, though less potent, vasodilating action to vasoactive intestinal peptide. The higher circulating levels of peptide histidine valine found in man suggest that it may be important in modulating vascular tone.
Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man
Authors: Olsen N. V. , Hansen J. M. , Ladefoged S. D. , Fogh-Andersen N. , Leyssac P. P.
Published: August 2015

1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates of sodium and water during dopamine infusion (3 μg min−1 kg−1) were estimated in 12 normal volunteers.

2. CNa increased by 128% (P <0.001). Effective renal plasma flow and GFR increased by 43% (P <0.001) and 9% (P <0.01), respectively. CLi increased in all subjects by, on average, 44% (P <0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P <0.001), and estimated absolute proximal reabsorption rate (GFR–CLi) decreased by 8% (P <0.01). Absolute distal sodium reabsorption rate [(CLi–CNa) × PNa, where PNa is plasma sodium concentration] increased (P <0.001), and fractional distal sodium reabsorption [(CLi–CNa)/CLi] decreased (P <0.001).

3. It is concluded that natriuresis during low-dose dopamine infusion is caused by an increased outflow of sodium from the proximal tubules that is not fully compensated for in the distal tubules.
Skeletal muscle metabolism in the leg during exercise in patients with congestive heart failure
Authors: Marie Pierre-Yves , Escanye Jean-Marie , Brunotte François , Robin Brigitte , Walker Paul , Zannad Faiez , Robert Jacques , Gilgenkrantz Jean-Marie
Published: August 2015

1. Using 31P nuclear magnetic resonance, it has previously been demonstrated that patients with congestive heart failure exhibit a greater than normal phosphocreatine (PCr) depletion in the working skeletal muscles of the arm. We have studied the importance of the work necessary to reach a similar PCr depletion {[PCr]/([PCr] + [Pi]) = 0.5} in calf muscle. Our results show significantly lower values for patients with congestive heart failure in both aerobic and ischaemic conditions (respectively: 0.009 ± 0.007 vs 0.026 ± 0.013 W/kg body weight, P <0.01; 0.29 ± 0.16 vs 0.90 ± 0.25 J/kg body weight, P <0.01).

2. This original model of skeletal muscle exercise facilitates a comparison of PCr recovery rate due to a similarity in the PCr depletion and intracellular pH in the two series at the start of recovery. However, the PCr recovery rate is similar after both normoxic and ischaemic exercise, i.e. respective percentages of PCr increase in the first 25 s recovery spectrum were: (a) aerobic exercise, congestive heart failure 133 ± 18%, control series 138 ± 18%; (b) ischaemic exercise, congestive heart failure 114 ± 13%, control series 118 ± 12%. The absence of a difference in PCr recovery rate and the greater PCr depletion by ischaemic work in patients with congestive heart failure suggest modifications that cannot be explained by a reduced blood flow to the muscle.

3. When comparing the two series, intracellular pH evolved similarly in normoxia and ischaemia during both work and recovery. Thus, no increase in anaerobic glycolytic activity appears when equivalent PCr depletion has occurred.
Changes in skin blood flow during the menstrual cycle: The influence of the menstrual cycle on the peripheral circulation in healthy female volunteers
Authors: Bartelink M. L. , Wollersheim H. , Theeuwes A. , van Duren D. , Thien Th.
Published: August 2015

1. It is known that females have a lower skin perfusion than males. In women there are also differences in blood flow at different reproductive stages of their lives. As an initial investigation of the possible contribution of sex hormones to these differences, we studied skin and forearm blood flow during the natural changes in hormone levels which occur during the menstrual cycle.

2. Thirty-one healthy female volunteers were studied. The effect of a standardized finger cooling test (immersion of a gloved hand in a 16°C water bath) on finger skin temperature and on laser Doppler flux in the finger, and forearm blood flow (strain gauge venous occlusion plethysmography) was assessed at four different times during one cycle: during menstruation, 1 day before ovulation, 2 days after ovulation and at the mid-luteal phase. Test days were determined by daily measurements of basal body temperature and were confirmed afterwards by determinations of serum luteinizing hormone, follicle-stimulating hormone, 17β-oestradiol and progesterone.

3. Peripheral skin circulation varied significantly within one menstrual cycle. The extremes were a mean finger skin temperature of 25.9 ± 3.0°C in the luteal phase compared with 28.4 ± 3.7°C in the pre-ovulatory phase (P = 0.002). The respective values for the mean laser Doppler flux were 18.4 ± 10.9 compared with 29.2 ± 16.4 arbitrary units (P = 0.003).

4. Baseline forearm muscle blood flow also varied significantly (P = 0.04) within one menstrual cycle, with low values in the menstrual phase compared with the other phases.

5. In conclusion, we have shown that peripheral skin circulation and forearm muscle blood flow exhibit significant variability during the hormonal changes in a menstrual cycle.
Ventilatory responses to hypercapnia and hypoxia in patients with eucapnic morbid obesity before and after weight loss
Authors: Chapman K. R. , Himal H. S. , Rebuck A. S.
Published: August 2015

1. To examine the relationship between eucapnic morbid obesity and ventilatory responsiveness to chemical stimuli, we measured hypercapnic and hypoxic ventilatory responses in 29 patients (26 women, three men) before and 3–6 months after gastroplasty. No subject demonstrated resting awake hypercapnia and none suffered from sleep-disordered breathing.

2. Mean weight fell significantly (122.8 ± 21.4 vs 102.2 ± 22.8 kg, P <0.0001) and functional residual capacity rose slightly but significantly (1.94 ± 0.58 vs 2.18 ± 0.64 litres; P <0.05) after weight loss.

3. The hypercapnic ventilatory response slope fell significantly after weight loss (2.88 ± 2.27 vs 2.24 ± 1.06 litres min−1 mmHg−1, P <0.05) with a significant shift of the ventilatory response curve to the right. There were no statistically significant changes in the patterns of ventilatory response.

4. In addition, isocapnic hypoxic ventilatory response slopes, measured at two levels of carbon dioxide partial pressure, fell significantly after weight loss. These changes were accompanied by significant shifts of the ventilatory response curves to the left, such that, for a given oxygen saturation, mean ventilation was significantly lower in the less obese state. Similarly to hypercapnic responses, there were no statistically significant changes in ventilatory pattern despite the changes in overall ventilatory response.

5. We conclude that ventilatory responsiveness to chemical simuli is increased in obese subjects who maintain adequate alveolar ventilation while awake.
Timing of deep breaths during rest and light exercise in man
Authors: Patil C. P. , Saunders K. B. , Sayers B. McA.
Published: August 2015

1. We used digital filtering techniques and segmental analysis to dissect a series of respiratory variables into three components: (a) outlying values, including deep breaths or sighs; (b) random variation; (c) non-stationary baseline variation.

2. Records of about 30 min breathing were obtained from normal adults at rest and at 50 W exercise.

3. Deep breaths were defined as having a tidal volume >2.5 sd above the mean.

4. We related these deep breaths to preceding trends in tidal volume and end-tidal partial pressure of CO2.

5. At rest, there was no relation between deep breaths and tidal volume, but the deep breaths were significantly clustered around the troughs in end-tidal partial pressure of CO2.

6. At 50 W exercise, there was no relation between deep breaths and end-tidal partial pressure of CO2, but the deep breaths were significantly clustered around tidal volume troughs.

7. Results obtained by pneumography were concordant with those obtained by using a mouthpiece to measure ventilation.
Ketone body metabolism in lean male adults during short-term starvation, with particular reference to forearm muscle metabolism
Authors: Elia M. , Wood S. , Khan K. , Pullicino E.
Published: August 2015

1. Thirty-three arteriovenous forearm catheterization studies were carried out in 19 lean subjects starving for 12–14 h(n = 13), 30–36 h (n = 7) and 60–66 h (n = 13). Forearm blood flow was measured in order to calculate the flux of various substrates. At the same time, whole-body oxidation of fat, carbohydrate and protein was calculated using indirect calorimetry and urinary nitrogen excretion.

2. After an overnight fast (12–14 h), whole-body resting energy expenditure was accounted for by the oxidation of protein (15%), carbohydrate (17%) and fat (68%). At 30–36 h and 60–66 h of starvation, essentially all the non-protein energy was derived from the oxidation of fat (directly plus indirectly via ketone bodies).

3. After an overnight fast, acetoacetate and 3-hydroxybutyrate were taken up by forearm muscle at a rate which could account for 5% of the resting O2 consumption of this tissue. As starvation progressed, forearm muscle took up more acetoacetate and released 3-hydroxybutyrate so that the net uptake of ketone bodies was sufficient to account for about 10% of the resting O2 consumption at 30–36 h of starvation and about 20% at 60–66 h of starvation.

4. The uptake of circulating non-esterified fatty acids by forearm muscle accounted for a greater proportion of the forearm O2 consumption than the uptake of ketone bodies at all times studied. The release of lactate and alanine was significantly greater at 36–40 h and 60–66 h of starvation compared with 12–14 h of starvation, but that of glucose did not change significantly.

5. The results suggest that during early starvation: (a) the release of 3-hydroxybutyrate by muscle (36–66 h starvation) contributes to the circulating 3-hydroxybutyrate concentration, (b) the contribution of ketone bodies to oxidative metabolism in lean subjects is variable but considerably lower than the generally accepted values in obese individuals, and (c) the dominant energy source for the resting muscle of lean individuals between 12 and 66 h of starvation is non-esterified fatty acids.
Cardiac output and oxygen uptake in patients with renal failure
Authors: Kong C. H. , Thompson F. D. , Imms F. J.
Published: August 2015

1. Cardiac index, oxygen uptake and haemoglobin concentration have been measured in eight patients with end-stage renal failure, and the values compared with those in eight healthy control subjects. Assuming the arterial blood to be 97% saturated, the oxygen saturation of mixed venous blood has been calculated.

2. Cardiac index was lower in the patients (2.45 ± 0.42 litres min−1 m−2) compared with the control subjects (3.74 ± 0.17 litres min−1 m−2). Oxygen uptake was reduced from 147 ± 16 ml STP min−1 m−2 in the control subjects to 112 ± 9 ml STP min−1 m−2 in the patients.

3. Oxygen saturation of mixed venous blood was 53 ± 8% in the patients compared with 79 ± 2% in the control subjects, suggesting some degree of tissue hypoxia. If oxygen uptake were not reduced in renal failure, then the mixed venous blood oxygen saturation would be as low as 40%.

4. The oxygen saturation of blood sampled from the superior vena cava of patients with renal failure was 57 ± 6%.

5. The data on oxygen uptake and venous oxygen saturation suggest that in the patients with end-stage renal failure, the low values of cardiac index, previously measured by impedance cardiography, are accurate.
Renal Acidification Defect Induced by Lithium in Control and Acidotic Rats
Authors: MacLaughin M. , Aires M. Mello
Published: August 2015

1. The aim of this work was to contribute to a better understanding of the mechanism by which Li+ administration impairs renal tubular acidification.

2. The kinetics of tubular acidification in the mid-proximal and distal convoluted tubules were studied by measuring intratubular pH using Sb microelectrodes during stopped-flow microperfusion with Krebs-Ringer bicarbonate (30 mmol/l) buffer. Four groups of male Wistar rats were utilized in this study: control, control plus lithium (C + Li+; one intraperitoneal injection of LiCl of 4 mmol l−1 day−1 kg−1 for 4 days), acidotic and acidotic plus lithium (A+ Li+).

3. In C + Li+ rats, the half-time of acidification was significantly higher than in control rats (P < 0.01), in both the mid-proximal tubule (11.3 ± 0.34 vs 6.73 ± 0.22 s) and the distal convoluted tubule (17.5 ± 0.31 vs 11.5 ± 1.02 s), and net HCO3− reabsorption was lower in both the mid-proximal tubule and the distal convoluted tubule. The effects of Li+ on tubular acidification kinetics were similar in acidotic rats.

4. A net Na+ flux, as measured by the Gertz split-droplet method, was significantly decreased in the mid-proximal tubule (P < 0.01) in C + Li+ rats compared with control rats (2.14 ± 0.17 vs 4.07 ± 0.39 nmol s−1 cm−2).

5. The transepithelial potential difference in the distal convoluted tubule was significantly lower (P < 0.01) in C + Li+ rats than in control rats (–7.50 ± 1.50 vs −20.5 ± 1.12 mV).

6. These findings suggest that Li+ causes a reduction in the apical Na+ gradients in both tubular segments, thereby decreasing the favourable driving force for H+ secretion.
Effect of Aspirin Infusions on Platelet Function in Humans
Authors: Wilson K. M. , Siebert D. M. , Duncan E. M. , Somogyi A. A. , Lloyd J. V. , Bochner F.
Published: August 2015

1. The inhibitory effects of aspirin on platelet function in vitro have been shown to be both time (over 3 h) and concentration (1–10 μmol/l) dependent.

2. To determine if these effects occurred in vivo, four volunteers received intravenous infusions on four occasions, to give constant plasma aspirin concentrations of 0, 1, 2 and 4 μmol/l over 3 h. Infusions were performed at intervals of at least 2 weeks.

3. Before and during the infusions, blood was taken for assay of aspirin concentrations, and measurements of platelet aggregation in response to collagen, adenosine 5′-pyrophosphate and arachidonate. Thromboxane generation after stimulated platelet aggregation and whole-blood coagulation was also measured.

4. At each aspirin concentration, both platelet aggregation and thromboxane generation in response to collagen and arachidonate were inhibited progressively over the 3 h infusion period. Greatest inhibition was seen during the 4 μmol/l infusion, which produced maximal or near-maximal inhibition by the third hour.

5. Thromboxane generated during whole-blood coagulation was similarly inhibited in both a time- and concentration-dependent manner throughout all aspirin infusions.

6. The progressive nature of the inhibition of platelet function with these low aspirin concentrations may be due to either slow aspirin transport across the platelet membrane or delayed interaction with cyclo-oxygenase.
Active and Inactive Urinary Kallikrein in Man: Effects of Diuresis and Antidiuresis
Authors: Waller Derek G. , Bhatia Satvinder S. , Campbell Sara K. , Albano Janet D. M. , Millar J. Gavin B.
Published: August 2015

1. The urinary excretion of active and inactive kallikrein was studied in volunteers during diuresis induced by water loading or oral frusemide and during antidiuresis induced by desamino-d-arginine-vasopressin.

2. During acute oral water loading, excretion of active kallikrein was unchanged, despite high urine flow rates and low urine osmolalities being achieved. Excretion of inactive kallikrein correlated with the urine flow rate.

3. After desamino-d-arginine-vasopressin in eight water-loaded and six normally hydrated subjects, excretion of inactive kallikrein also correlated with the urine flow rate. There were no significant changes in the excretion of active kallikrein.

4. After frusemide there was a small transient increase in excretion of active kallikrein 1–2 h after dosing which coincided with the maximum diuresis and natriuresis. Excretion of inactive kallikrein again correlated with urine flow rate but the regression relationship between the two variables was different for water-load-induced and frusemide-induced diuresis.

5. These studies do not support a role for urinary kallikrein in the modulation of the antidiuretic action of vasopressin, but suggest that it may contribute to the natriuretic action of frusemide.
Haemodynamic and Metabolic Effects of Infused Adenosine in Man
Authors: Edlund Anders , Sollevi Alf , Linde Birgitta
Published: August 2015

1. Haemodynamic and metabolic effects of intravenous infusion of adenosine, an endogenous vasodilator, were studied in healthy humans.

2. Catheters were inserted into pulmonary and brachial arteries and into the hepatic and subclavian veins. Cardiac output was determined according to the Fick principle, and splanchnic blood flow was measured by using extraction of Indocyanine Green. Skin blood flow was estimated by a laser Doppler technique, calf blood flow by venous occlusion plethysmography and skeletal muscle and adipose tissue blood flow by a local isotope clearance technique.

3. Adenosine (infused in steps from 40 to 80 μg min−-1 kg−-1 into a central vein) elicited a gradual reduction in the peripheral vascular resistance to less than 50% of the basal level. There was a slight increase in the systemic blood pressure, but the pulmonary arterial and the ventricular filling pressures were unchanged. Cardiac output was doubled, accomplished by a combination of a positive chronotropic effect and an increase in stroke volume, which may be secondary to diminished peripheral resistance.

4. Skin blood flow increased by 100% at 50 μg of adenosine min−-1 kg−-1, whereas splanchnic blood flow rose significantly at 60 μg of adenosine min−-1 kg−-1. Blood flow in the calf, gastrocnemius muscle and adipose tissue did not change significantly.

5. Arterial concentrations of noradrenaline and adrenaline increased by 62 and 43%, respectively, during infusion of adenosine. Arterial levels of glycerol were depressed by more than 50%, but those of glucose and pyruvate were unchanged.

6. In conclusion, exogenous adenosine caused a marked systemic vasodilatation, with different responsiveness in the investigated vascular beds. The vasodilatation occurred in the presence of an increase in generalized sympathetic activity. Adipose tissue blood flow was unaltered despite a considerable reduction in fat mobilization.
Response of Serum Interleukin-6 in Patients Undergoing Elective Surgery of Varying Severity
Authors: Cruickshank A. M. , Fraser W. D. , Burns H. J. G. , Van Damme J. , Shenkin A.
Published: August 2015

1. Recent studies have suggested that interleukin-6 is a major mediator of the acute-phase protein response in man. The aim of the present study was to investigate the relationships between the response of serum interleukin-6 to surgery, the type of surgical procedure performed and the response of serum C-reactive protein.

2. Timed venous blood samples were taken from 26 patients in five broad surgical categories (minor surgery, cholecystectomy, hip replacement, colorectal surgery and major vascular surgery). C-reactive protein and interleukin-6 were measured in each sample.

3. Serum interleukin-6 rose within 2–4 h of incision in all patients and the magnitude of the response differed among the various surgical groups. The response of interleukin-6 correlated (r = 0.80, P < 0.001) with the duration of surgery. In contrast, serum C-reactive protein was not detectable after minor surgery (< 10 mg/l) and the response of C-reactive protein did not differ among the more major surgical groups. The response of interleukin-6 showed a weak, but significant, correlation with the response of C-reactive protein (r = 0.67, P < 0.001).

4. We conclude that serum interleukin-6 is a sensitive, early marker of tissue damage. In general, the greater the surgical trauma, the greater the response of serum interleukin-6 and the greater the peak serum concentration of interleukin-6. Our results are consistent with a role for interleukin-6 in the induction of C-reactive protein synthesis.