bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine receptors in papilla of human kidneys
Authors: Woodcock Elizabeth A. , Leung Edward , Johnston Colin I.
Published: August 2015

1. Adenylate cyclase activity in homogenates of human papillae was stimulated by adenosine agonist compounds.

2. The rank order of agonist potencies for stimulation was 5′-N-ethylcarboxamidoadenosine > l-N6-phenylisopropyladenosine > 2-chloroadenosine > N6-cyclohexyladenosine > d-N6-phenylisopropyladenosine. This order of agonist potencies is similar to that observed at adenylate cyclase-coupled A2-adenosine receptors in many different tissues.

3. The methylxanthines 8-phenyltheophylline and 1,3-diethyl-8-phenylxanthine acted as competitive antagonists, with 1,3-diethyl-8-phenylxanthine being approximately 10 times more potent than 8-phenyltheophylline.

4. This study demonstrates the presence of A2-adenosine receptors in the papilla of human kidney. These receptors are similar to adenosine receptors previously observed in the renal papillae of the rat in terms of both agonist and antagonist potencies.
Plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-containing superoxide dismutase in alcoholics treated with disulfiram
Authors: Öhman Michael , Marklund Stefan L.
Published: August 2015

1. Disulfiram has long been used in the treatment of chronic alcoholism. It is in vivo partially reduced to diethyldithiocarbamate, which is an efficient inhibitor of Cu, Zn-containing superoxide dismutase both in vitro and in vivo. The recently described extracellular superoxide dismutase is even more sensitive to diethyldithiocarbamate than Cu, Zn-superoxide dismutase.

2. To test for the possibility that long term treatment with disulfiram leads to inhibition of the superoxide dismutases, plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-superoxide dismutase were determined in 12 disulfiram-treated alcoholics, and compared with 11 non-treated alcoholics and 19 healthy controls.

3. Plasma extracellular superoxide dismutase was moderately reduced (about 20%) in the disulfiram-treated alcoholics as compared with the non-treated alcoholics and the healthy controls. No effect of disulfiram treatment on erythrocyte Cu, Zn-superoxide dismutase activity was demonstrated.
Metabolic rate after massive weight loss in human obesity
Authors: Finer Nicholas , Swan Philip C. , Mitchell Fred T.
Published: August 2015

1. Resting metabolic rate, measured by the ventilated hood technique in 11 obese subjects before weight loss was 6.5 ± 0.3 kJ/min, not significantly different from the value predicted by regression equations relating metabolic rate to body weight (established from measurements in 106 subjects).

2. After 34.5 kg mean weight loss, and during continued dieting, resting metabolic rate fell an average of 25% to 5.0 ± 0.18 kJ/min, significantly below that predicted for the new slimmed weight.

3. The fall in metabolic rate, over and above that expected from weight loss alone, suggests that the slimmed obese are hypometabolic compared with subjects of the same weight who have not lost weight.

4. The failure of the slimmed obese to maintain their weight loss is unlikely to be due solely to this excessive fall in resting metabolic rate, since they still had quantitatively higher energy expenditure than lean subjects.
Protein losing enteropathy associated with Nippostrongylus brasiliensis infestation and its impact on albumin homoeostasis in rats fed two levels of dietary protein
Authors: Lunn P. G. , Northrop C. A. , Behrens R. H. , Martin J. , Wainwright M.
Published: August 2015

1. Alterations in plasma albumin concentration and gastrointestinal permeability have been investigated in rats infected with the nematode Nippostrongylus brasiliensis and fed adequate or low protein diets.

2. Infection caused only minor changes in growth and food consumption of well nourished rats but resulted in significant reductions in those fed the low protein diet.

3. Animals in both dietary groups were able to mount an immune response beyond day 10 postinfection (p.i.) which caused expulsion of the parasites, but this was less effective in rats fed the low protein food.

4. Uninfected rats fed the low protein diet had significantly lower plasma albumin concentrations than their well nourished counterparts. Animals of both dietary groups showed a progressive reduction in plasma albumin concentration as the infection developed but values returned towards normal as the parasites were expelled.

5. The reduction in plasma albumin concentration was closely associated with increases in gastrointestinal leakage of plasma protein but losses were far greater in the protein deficiency animals. Beyond day 10 p.i. protein loss decreased in both dietary groups and by day 21 p.i. had returned to normal in well nourished animals but not those fed the low protein diet.

6. Intestinal permeability measured by the lactulose:mannitol ratio technique gave similar results to the protein loss data. Permeability increased as the infection progressed then fell as the worms were expelled but remained above control values in infected protein deficient animals.

7. Overall, animals fed the low protein diet were more severely affected by the parasite than were their well fed counterparts. The data clearly demonstrated that the combined effects of infection and dietary deficiency resulted in a more severe reduction in plasma albumin values than either factor produced alone. The results are discussed with reference to the aetiology of hypoalbuminaemia and kwashiorkor in man.
Sympathetic reflex control of subcutaneous blood flow in patients with congestive heart failure
Authors: Kassis Eli , Amtorp Ole , Skagen Knud
Published: August 2015

1. Central and local regulation of forearm subcutaneous vascular resistance (FSVR) during postural changes were studied in congestive heart failure (CHF). Blood flow was measured by the local 133Xe-washout technique. Nine patients with severe CHF (baseline angiographic ejection fraction, 23 ± 2%, mean ± sem; cardiac index, 2.2 ± 0.2 litres min−1 m−2; increased left ventricular pressures and dimensions) were compared with seven control subjects who had normal cardiac performance.

2. Baseline FSVR and plasma concentrations of noradrenaline and adrenaline were substantially higher in patients with CHF than control subjects. However, the patients, like control subjects, increased FSVR by 46 ± 3% in response to increase in local venous transmural pressure and disclosed a normal response to decrease in forearm perfusion pressure. Both responses to changes in vascular transmural pressure were preserved after either proximal nervous blockade or local β-receptor blockade.

3. Central sympathetic stimulation was induced with use of 45° upright tilt. Control subjects developed vasoconstriction (FSVR increased by 59 ± 5%), which was completely abolished after proximal nerve blockade. Patients with CHF developed vasodilatation (FSVR decreased by 24 ± 8%), which was not only abolished but reversed after proximal nerve blockade (FSVR increased by 22 ± 7%), probably owing to the increased humoral vasoconstrictor activity. The paradoxical vasodilator response to central sympathetic stimulation in these patients was reversed after local β-receptor blockade (FSVR increased by 19 ± 9%).

4. The local vasoconstrictor reflex responsiveness and intrinsic vascular reactivity were not affected by the augmented baseline sympathetic vasoconstrictor activity in patients with CHF. Central sympathetic stimulation seems to elicit a β-adrenergic reflex effect intended to improve perfusion of the subcutaneous tissue in these patients.
Effects of somatostatin, naloxone and prochlorperazine on the control of ventilation in man
Authors: Maxwell D. L. , Nolop K. B. , Hughes J. M. B.
Published: August 2015

1. In seven normal subjects the ventilatory responses to progressive isocapnic hypoxia and hyperoxic hypercapnia were measured during rebreathing.

2. During an infusion of somatostatin (10 nmol/mm) the mean hypoxic response decreased by 66% (control: − 1.6 sd 1.2 litres min−1 %−1Sao2: somatostatin: − 0.6 sd 0.7) but the mean hypercapnic response was unchanged (control: 2.0 sd 0.8 litre min−1 mmHg−1; somatostatin: 2.3 sd 1.2). There was no change in resting V˙O2 or V˙CO2 during somatostatin infusion.

3. The opiate antagonist, naloxone (0.1 mg/kg, intravenously), caused little change in either response (mean hypoxic response: − 1.7 sd 1.0 litre min−1 %−1Sao2; mean hypercapnic response: 2.4 sd 0.9 litre min−1 mmHg−1).

4. In five of the subjects the dopamine antagonist, prochlorperazine (10 mg, intravenously), increased the mean hypoxic response by 134% (control: − 1.9 sd 1.4 litres min−1 %−1Sao2; after prochlorperazine: − 3.8 sd 1.6; P < 0.05). The mean hypercapnic response after this drug was also increased (control: 2.1 sd 1.0 litre min−1 mmHg−1; after prochlorperazine: 3.1 sd 1.0) but this change did not achieve significance.

5. The selective effect of somatostatin on the hypoxic response, suggestive of an action on the carotid body, was not inhibited by prior injection of either naloxone or prochlorperazine, and its mode of action remains to be found.
Effects of mucosal removal on guinea-pig airway smooth muscle responsiveness
Authors: Murlas Christopher
Published: August 2015

1. The contractile response to histamine, acetylcholine (ACh), KCl or electrical field stimulation (EFS) was examined in paired tracheal rings (one of each being denuded by mucosal rubbing), which were mounted in muscle chambers filled with a continuously aerated physiological salt solution at 37°C.

2. Removal of the respiratory mucosa increased the sensitivity of airway muscle to ACh, histamine and EFS, but not to KCl. The hypersensitivity of denuded rings to histamine and EFS was greater than to ACh. Atropine reduced the histamine hypersensitivity observed.

3. Pretreating intact preparations with indomethacin augmented their responsiveness to EFS, histamine and ACh.

4. Indomethacin augmentation of histamine- and EFS-induced responses was greater in preparations without epithelium.

5. We conclude that the airway mucosa may be associated with a factor that reduces airway smooth muscle responsiveness to stimulation.
Glucose oxidation rates in newborn infants measured with indirect calorimetry and [U-13Clglucose
Authors: Sauer P. J. J. , Van Aerde J. E. E. , Pencharz P. B. , Smith J. M. , Swyer P. R.
Published: August 2015

1. Indirect calorimetry and primed constant infusion of [U-13C]glucose were combined in 16 appropriate-for-gestational age newborn, parenterally fed infants, in order to measure glucose utilization and glucose oxidation respectively.

2. Glucose intake ranged between 10.0 and 24.1 g day−1 kg−1 and energy intake between 156.9 and 439.3 kJ day−1 kg−1.

3. Glucose utilization (P < 0.001), glucose oxidation (P < 0.001) and metabolic rate (P < 0.005) increased significantly with rising glucose intake.

4. The significant difference between glucose utilization and oxidation (P < 0.001) can be accounted for by an increasing storage as fat.

5. As lipogenesis from glucose consumes 15-24% of the original glucose energy, the increasing metabolic rate accompanying rising glucose intake is probably due to increasing lipogenesis.
Cation transport abnormalities in vivo in untreated essential hypertension
Authors: Boon Nicholas A. , Aronson Jeffrey K. , Hallis Keith F. , Grahame-Smith David G.
Published: August 2015

1. In order to study cation transport in vivo we have measured the changes in plasma and intra-erythrocytic rubidium concentrations after the oral administration of rubidium chloride.

2. In this paper we describe our findings in 22 patients with untreated essential hypertension, compared with the findings in 22 carefully matched control subjects. Our findings in patients receiving short-term digoxin therapy and in patients with chronic renal failure are also included for comparison.

3. Whereas the findings in patients receiving digoxin and in patients with chronic renal failure are compatible with a widespread reduction in sodium, potassium-ATPase activity in vivo, the findings in patients with untreated essential hypertension are not.

4. Further analysis of the data and a similar study of the disposition of 42K after the intravenous administration of 42KC1 suggest that in vivo net cation transport is enhanced in the erythrocytes of patients with untreated essential hypertension.
Lactulose 51Cr-labelled ethylenediaminetetra-acetate, l-rhamnose and polyethyleneglycol 500 as probe markers for assessment in vivo of human intestinal permeability
Authors: Maxton D. G. , Bjarnason I. , Reynolds A. P. , Catt S. D. , Peters T. J. , Menzies I. S.
Published: August 2015

1. The urinary excretion of lactulose, 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), l-rhamnose and polyethyleneglycol 400 (PEG-400) has been measured after intravenous and oral administration in healthy volunteers.

2. Intestinal permeation of the probes was compared after their ingestion in iso-osmolar, hyperosmolar and cetrimide-containing test solutions.

3. Urinary recovery of lactulose and 51Cr-EDTA after intravenous administration reached 75% by 5 h, and exceeded 90% at 24 h, and these values were 62 and 72%, respectively, for l-rhamnose. Recovery of PEG-400, however, varied with the relative molecular mass (Mr) of each polymer from 25.9 to 68.5% in 24 h.

4. Intestinal permeation of ingested lactulose and 51Cr-EDTA was low, but that of L-rhamnose was 45-fold, and that of PEG-400 100-fold, greater. Permeation of lactulose and 51Cr-EDTA was markedly increased by cetrimide and hyperosmolar stress, whereas that of l-rhamnose showed little change. PEG-400 permeation was not affected by cetrimide, but was slightly increased by hyperosmolar stress.

5. The 5 h permeation of lactulose, but not of l-rhamnose or PEG-400, correlated with that of 51Cr-EDTA (r = 0.98, P < 0.001).

6. These findings are compatible with three distinct pathways of unmediated mucosal permeation, l-rhamnose (radius < 0.4 nm) passing mainly through small aqueous ‘pores’ of high incidence, lactulose and 51Cr-EDTA (radius > 0.5 nm) through larger aqueous ‘channels' of low incidence susceptible to cetrimide and hyperosmolar stress, and PEG-400, which has appreciable lipid solubility, by partition through cell membrane lipid as well as the aqueous ‘pores’.
Assessment of the sensitivity of leukaemic cells to cytotoxic drugs by bioluminescence measurement of ATP in cultured cells
Authors: Kuzmits Rudolf , Aiginger Paul , Müller Matthias M. , Steurer Günter , Linkesch Werner
Published: August 2015

1. A short-term test in vitro is described, which can be used to detect resistance to cytostatic agents in leukaemic cells. Leukaemic cell suspensions were incubated with cytostatic agents and the resulting intracellular ATP concentrations were measured by a bioluminescence ATP assay.

2. There was a clear dose-effect relationship in acute leukaemia and chronic lymphocytic leukaemia cells for drugs used in the treatment of leukaemias. A good correlation was found between the ATP content of leukaemic cells and cell viability as determined by the trypan blue dye exclusion test.

3. Preliminary individual clinical correlations suggest a correlation between the chemosensitivity in vitro and the response patterns in vivo in leukaemia patients. This simple, fast and sensitive method may have application for determination of drug-induced cytotoxicity in leukaemic cells in vitro.
Evidence for extrarenal metabolism of 25-hydroxyvitamin D3 in man
Authors: Fraher L. J. , Adami S. , Papapoulos S. E. , Sudan H. L. , McGonigle R. J. , Parsons V. , O'Riordan J. L. H.
Published: August 2015

1. Metabolites of vitamin D3 were measured in the circulation of four patients on chronic haemodialysis (three of whom were surgically anephric) before and during daily ingestion of 40000 i.u. of cholecalciferol.

2. Circulating 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] was measurable, but abnormally low before treatment; its circulating concentration rose in a substrate dependent manner when serum 25-hydroxyvitamin D3 (25-OHD3) increased, but the response was reduced when compared with the normal relationship.

3. Serum 1,25-hydroxyvitamin D3 [1,25-(OH)2D3] and calcidiol lactone (25-OHD3-lactone) were consistently unmeasurable in sera from these patients before administration of cholecalciferol. However, when serum 25-OHD3 rose with treatment, 1,25-(OH)2D3 became detectable in the sera of three of the four patients and 25-OHD3-lactone could be measured in all of them.

4. These data indicate that extrarenal sites of synthesis of 24,25-(OH)2D3, 25-OHD3-lactone and 1,25-(OH)2D3 exist in chronically dialysed patients but require large amounts of substrate to be significant.
Selective renal medullary damage and hypertension in the rat: The role of vasopressin
Authors: Russell G. I. , Godfrey N. P. , Forsling M. L. , Bing R. F. , Thurston H. , Swales J. D.
Published: August 2015

1. The induction of selective renal medullary damage by 2-bromoethylamine hydrobromide (BEA) results in polyuria and raised blood pressure. In view of the likely elevation of plasma vasopressin we have investigated the role of vasopressin (AVP) in the elevated blood pressure in this model.

2. Plasma vasopressin levels in BEA pretreated rats were raised significantly (2 ± 0.6 pg/ml vs 0.8 ± 0.1 in normal rat, P < 0.05) but not to pressor levels.

3. In addition, pressor responsiveness was investigated in renal medullary damaged rats. There was a reduced response to vasopressin and noradrenaline but no alteration with angiotensin II. A specific V1 receptor AVP antagonist [d(CH2)5Tyr(Me)AVP] produced no fall in blood pressure but returned the noradrenaline dose-response curve to normal. This suggests an interaction between vasopressin and the sympathetic nervous system in this model.

4. Thus there is no evidence that vasopressin contributes to the rise in blood pressure produced by chemical renal medullectomy and other mechanisms have to be sought.
Plasma noradrenaline in Goldblatt models of renovascular hypertension in the rat, before and after surgical reversal
Authors: Walker S. M. , Bing R. F. , Swales J. D. , Thurston H.
Published: August 2015

1. Plasma noradrenaline (NA), blood pressure (BP) and heart rate (HR) were measured simultaneously in conscious rats under basal conditions in the early phase (4–6 weeks) of one-kidney, one-clip hypertension (1K1C), in the early (4–6 weeks) and chronic (> 16 weeks) phases of the two-kidney, one-clip model (2K1C) and in age-matched loose clip control animals before and 2 days after unclipping.

2. The elevated BP in all three hypertensive groups fell to normal after unclipping, whereas removal of the constricting clip in loose clip controls had no effect on BP.

3. Plasma NA was elevated in 1K1C hypertension (P < 0.05) and fell slightly but non-significantly on unclipping. However, in the early phase of 2K1C hypertension plasma NA was unaltered before and rose significantly (P < 0.05) after unclipping. Plasma NA did not change with unclipping in the chronic phase of 2K1C hypertension and was not different from controls. Unclipping loose clip control animals produced no change in plasma NA.

4. Changes in HR on unclipping followed a similar pattern to changes in plasma NA: changes in the two variables were significantly correlated in all three models (1K1C: r = 0.61, P < 0.005; early 2K1C: r = 0.45, P < 0.05; chronic 2K1C: r = 0.62, P < 0.01). However, BP was only correlated with plasma NA in 1K1C hypertension (r = 0.49, P < 0.02) and not in either phase of the 2K1C model. There was also a highly significant correlation between HR and plasma NA in 1K1C hypertension (r = 0.71, P < 0.001). The pattern of the changes in plasma NA and HR that occurred with reversal of 1K1C hypertension was significantly different from those in the early phase 2K1C model (P < 0.05).

5. These data suggest that there is sympathetic nervous system (SNS) activation in the early phase of 1K1C hypertension, but provide no evidence for increased sympathetic activity in either the early or chronic phases of the 2K1C model. Neither do they support the hypothesis that the fall in BP with unclipping in this model is mediated by reduced SNS activity.
Ion transport in hypertension: are changes in the cell membrane responsible?
Authors: Bing Robert F. , Heagerty Anthony M. , Thurston Herbert , Swales John D.
Published: August 2015

Disturbances in several, distinct cell membrane ion transport processes have been demonstrated in essential hypertension but their variable relationship to blood pressure in different populations has made it difficult to achieve a unifying hypothesis. We suggest that altered composition of the lipid fraction of the cell membrane is the common underlying factor. This would produce many of the reported perturbations of cell membrane properties and function, not all of which relate directly to the development of hypertension, but which act as markers for the underlying abnormality. However, functions such as phosphoinositol turnover, calcium binding and Ca2+,Mg2+-ATPase dependent calcium efflux, which are influenced by the lipid composition of the membrane, provide a possible link between the membrane disturbance, intracellular calcium, vascular smooth muscle contraction and blood pressure. Alteration in the lipid content of the cell membrane not only provides an explanation for the variability in the ion transport abnormalities between populations but perhaps also for some of the variability in blood pressure within a single population. It also provides a potential means of influencing blood pressure by dietary intervention.
Altered extracellular calcium homoeostasis in essential hypertension: A consequence of abnormal cell calcium handling
Authors: Strazzullo P. , Galletti F. , Cirillo M. , Siani A. , Nunziata V. , Giannattasio R. , Mancini M.
Published: August 2015

1. A number of abnormalities in the extracellular and intracellular handling of calcium in arterial hypertension, namely an increased urinary calcium excretion, a reduced serum ionized calcium level and an enhanced intracellular free calcium concentration, have previously been reported by this and other laboratories.

2. The present study aimed to investigate the handling of an exogenous calcium load in hypertensive and normotensive subjects in order to detect possible differences with regard to tissue calcium metabolism in vivo.

3. A constant rate intravenous calcium infusion (0.2 mmol 2 h−1 kg−1 body wt.) was carried out in the participants. Serum calcium concentrations were determined at regular intervals during the infusion and in the 4 h after the end of the calcium load. Over the same period, urinary calcium excretion was evaluated in timed urine collections.

4. Hypertensive subjects had lower serum ionized calcium levels compared with normotensive subjects at all the experimental points, a finding suggestive of a faster disappearance of calcium from the circulation. The total body calcium clearance, calculated from the area under the curve of the serum calcium concentrations, was enhanced in hypertensive patients (P < 0.03).

5. Although the renal calcium excretion was higher in hypertension, the renal calcium clearance accounted for only a minor fraction of the total body clearance, suggesting that the reduced serum calcium levels achieved by the hypertensive patients were not explained by the renal calcium leak.

6. The enhanced total body calcium clearance found in hypertensive subjects is therefore due to an increased tissue calcium uptake. This finding provides indirect evidence of an altered cell calcium handling in hypertension.
Atrial natriuretic peptide: Physiological release associated with natriuresis during water immersion in man
Authors: Anderson J. V. , Millar N. D. , O'Hare J. P. , MacKenzie J. C. , Corrall R. J. M. , Bloom S. R.
Published: August 2015

1. Thermoneutral water immersion produces a physiological increase of thoracic blood volume, raises central venous pressure and increases urinary sodium excretion by a hitherto ill-understood mechanism. We have investigated whether this enhanced sodium excretion could be mediated by the recently discovered natriuretic factor, atrial natriuretic peptide (ANP).

2. During water immersion there was a highly significant (P < 0.001) twofold increase of the mean plasma ANP concentration and a doubling of the mean urinary sodium excretion. Both were unchanged during the control experiments.

3. These results are consistent with the hypotheses (a) that ANP is released into plasma in response to central blood volume expansion and (b) that it functions as a natriuretic hormone in normal man under physiological conditions.
The combined effects of two pairs of mediators, adenosine with methacholine and prostaglandin D2 with histamine, on airway calibre in asthma
Authors: Hardy C. C. , Braddeng P. , Robinson C. , Holgate S. T.
Published: August 2015

1. Mediators released from mast cells and secondary effector cells in the airways contribute to bronchoconstriction of allergic asthma. This study investigates methods for defining the effect of two inflammatory mediators on airway calibre in asthma.

2. In an initial study on three asthmatic subjects, subconstrictor (subthreshold) concentrations of two mast cell derived mediators, histamine and prostaglandin (PG) D2, produced similar displacement to the left of a histamine concentration–specific airways conductance (sGaw) response curve. With both agonists enhancement of histamine-induced bronchoconstriction was greater at low histamine concentrations. Since potentiation of histamine-induced bronchoconstriction was independent of the class of subconstrictor agent given, it is likely to represent a physiological rather than a pharmacological interaction.

3. During provoked asthma different constrictor mediators are likely to be released simultaneously into the airways. A method was therefore devised to investigate the combined effect of equiconstrictor concentrations of two mediators on airway calibre.

4. Two pairs of inhaled bronchoconstrictor agonists were chosen for study: adenosine with methacholine and PGD2 with histamine. For each agonist, concentration–sGaw response curves were constructed, from which were derived the provocation concentrations of agonist causing a 25% fall in sGaw from baseline (PC25) and required to further this to 50%(PC50_25).

5. On separate days, eight subjects received paired inhalations of methacholine–adenosine, methacholine–methacholine and adenosine–adenosine. The concentration used for the first inhalation was the PC25 value and for the second inhalation the PC50_25 value. Before, immediately after the first inhalation, and at regular intervals after the second inhalation, sGaw was followed for 30 min. In seven subjects the study was repeated, replacing methacholine with PGD2 and adenosine with histamine.

6. When methacholine was combined with adenosine, and PGD2 was combined with histamine the maximum falls in sGaw and rates of recovery after inhalation of the second mediator were not statistically different from those values observed with paired inhalations of the same mediators.

7. Thus, employing pharmacologically active concentrations of two pairs of constrictor mediators, which act through separate receptor mechanisms, we have been unable to demonstrate any pharmacological interaction on airway calibre in asthma.
Impaired sodium excretion in response to volume expansion induced by water immersion in insulin-dependent diabetes mellitus
Authors: O'Hare J. P. , Roland J. M. , Walters G. , Corrall R. J. M.
Published: August 2015

1. The renal response to volume expansion produced by water immersion to the neck at 35°C was examined in eight young normotensive uncomplicated insulin-dependent diabetic subjects and in eight matched normal control subjects.

2. Both the diabetic and normal subjects manifested a renal response of natriuresis and kaliuresis on immersion, but the natriuretic response was reduced in the diabetic group. Thus the induced excretion of sodium over the 4 h of immersion was 40 ± 5 mmol (mean ± sem) in the normal group compared with 22 ± 4 mmol in the diabetic group (P < 0.02).

3. In the normal subjects creatinine clearance did not change during immersion compared with pre-immersion control values while in the diabetic group it rose from pre-immersion control values of 112 ± 11 ml/min to a mean value of 127 ± 11 ml/min during immersion (P < 0.01).

4. The diabetic subjects thus excreted less sodium despite an increased filtered load during water immersion. Fractional excretion of sodium was significantly reduced in the diabetic subjects compared with the normal control subjects (P < 0.05).

5. The suppression of plasma renin and aldosterone was similar in normal and diabetic groups.

6. Tubular sodium retention could be an early functional change in the diabetic kidney, and be implicated in the development of diabetic nephropathy.
Effect of ganglionic blockade on endogenous circulating pancreatic polypeptide, vasoactive intestinal polypeptide, substance P, neurotensin and noradrenaline in healthy controls and long-term insulin-dependent diabetic patients
Authors: Kastrup Jens , Henrksen Jens H. , Pedersen Jesper Holst , Fahrenkrug Jan , Schaffalitzky de Muckadell Ove B. , Schwartz Thue , Parving Hans-Henrik , Christensen Niels Juel
Published: August 2015

1. Plasma pancreatic polypeptide (PP), vasoactive intestinal polypeptide (VIP), substance P (SP), neurotensin (NT) and noradrenaline (NA) were measured in eight healthy subjects and 12 long-term insulin-dependent diabetic patients with and without autonomic neuropathy, before and after intravenous infusion of the ganglionic blocking agent trimethaphan camsylate, in order to determine the influence of the autonomic nervous system on the baseline values of the substances.

2. The basal levels of the measured substances were not significantly different in healthy subjects and patients with or without diabetic autonomic neuropathy.

3. In healthy subjects, the ganglionic blockade induced a significant decrease in PP (80%) (P < 0.02), NA (58%) (P <0.05), NT (27%) (P < 0.05) and a significant increase in SP (30%) (P < 0.05), while the VIP concentration remained unchanged.

4. The diabetic patients had nearly the same significant decrease in PP (68%) (P < 0.01), NA (50%) (P < 0.01), NT (22%) (P < 0.02), VIP (21%) (P < 0.05) and increase in SP (73%) (P < 0.01). No relationship was found between the autonomic neuropathy and changes of the substances during ganglionic blockade.

5. The results indicate that the postganglionic part of the autonomic nervous system participates in the maintenance of a normal baseline level of PP, NT and NA, but not of VIP. The regulation of VIP may be disturbed in long-term diabetic subjects.
The exchange of blood-borne amino acids in the leg during abdominal surgical trauma: Effects of glucose infusion
Authors: Lund J. , Stjernström H. , Bergholm U. , Jorfeldt L. , Vinnars E. , Wiklund L.
Published: August 2015

1. The exchange of plasma amino acids and glucose, lactate, glycerol and 3-hydroxybutyrate in the leg was studied in otherwise healthy patients undergoing elective cholecystectomy.

2. Seven patients were given a constant intravenous infusion of glucose at a rate of 1.1 mmol/min throughout the study. Seven other patients who received normal saline only served as a control group.

3. Measurement of leg blood flow and arterio-femoral venous differences of amino acids and other energy metabolites were made on four occasions: (I) before surgery, (II) 10 min after skin incision, (III) at the end of surgery, and (IV) 30 min after the end of anaesthesia.

4. The release of amino acids from the leg was comparable in the two groups before and during the early part of surgery. At the end of surgery the release of several individual amino acids, as well as the total release of amino acids, from the leg was higher in the patients given glucose infusion compared with the control patients.

5. The infusion of glucose prevented the intraoperative rise in arterial levels and uptake of 3-hydroxybutyrate in the leg. A high release of amino acids at the end of surgery was thus associated with low arterial levels of 3-hydroxybutyrate while the reverse pattern was seen in the control patients.

6. These effects of glucose infusion were qualitatively different from those seen in uninjured post-absorptive man.
Chlorpropamide–alcohol flush reaction and isoenzyme profiles of alcohol dehydrogenase and aldehyde dehydrogenase
Authors: Johnston C. , Saunders J. B. , Barnett A. H. , Ricciardi B. R. , Hopkinson D. A. , Pyke D. A.
Published: August 2015

1. To investigate the enzymatic basis of the chlorpropamide–alcohol flush reaction (CPAF) we compared the isoenzyme profiles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) from liver biopsies, and of ALDH alone from erythrocytes and leucocytes, in CPAF-positive and CPAF-negative subjects.

2. No differences were seen in ADH or ALDH phenotypes, or in the relative activities of the isoenzymes, between the two groups before chlorpropamide was given; in particular, no subjects showed the ‘null’ ALDH phenotype that is associated with the alcohol flush reaction in oriental subjects.

3. There was a significant decrease in erythrocyte ALDH activity after 7 days' treatment with chlorpropamide in CPAF-positive individuals but no such difference was seen in CPAF-negative subjects.

4. These results indicate that CPAF has a different enzymatic basis from the alcohol flush reaction of oriental subjects and suggest that in CPAF-positive subjects erythrocyte ALDH may be particularly susceptible to inhibition by chlorpropamide.
Respiratory and cardiovascular effects of central and peripheral intravenous injections of capsaicin in man: Evidence for pulmonary chemosensitivity
Authors: Winning A. J. , Hamilton R. D. , Shea S. A. , Guz A.
Published: August 2015

1. The respiratory and cardiovascular effects of capsaicin injection into the superior vena cava and an arm vein were studied in three normal subjects.

2. No changes were seen in tidal volume, inspiratory time or expiratory time after capsaicin injection. Instantaneous heart rate, systolic blood pressure and diastolic blood pressure remained unchanged.

3. Central and peripheral intravenous injections of capsaicin but not control solution above a threshold of 0.5 μg/kg produced dose-dependent sensations sequentially in the chest, face, rectum and extremities. The chest sensation, a ‘raw, burning’ feeling, occurred 3–4 s after central capsaicin injection. No subject reported feeling breathless. In one subject the maximum tolerable dose of capsaicin (4 μg/kg) produced paroxysmal coughing 3.9 s after a central injection.

4. In two of the subjects capsaicin injection was repeated after inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter 4.8, μm), sufficient to block the cough reflex to a 5% citric acid aerosol. Prior inhalation of local anaesthetic aerosol abolished the chest sensation after capsaicin injection; the other sensations were unaffected.

5. This study demonstrates that stimulation of receptors accessible from the pulmonary vascular bed does not evoke the pulmonary chemoreflex in conscious man but can produce coughing. It provides evidence for the existence of a nociceptive system of nerve endings in the lung parenchyma that can be blocked by inhaled local anaesthetic aerosol.
Vasopressin and catecholamine secretion during apomorphine-induced nausea mediate acute changes in haemostatic function in man
Authors: Grant P. J. , Hughes J. R. , Dean H. G. , Davies J. A. , Prentice C. R. M.
Published: August 2015

1. Seven male volunteers were given apomorphine (14–20 μg/kg) subcutaneously on a total of ten occasions. Nausea was experienced on six occasions and on four occasions there was no effect.

2. Venous samples were taken before injection, at peak nausea and 20 min later for assay of factor VIII coagulant activity (FVIIIC), von Willebrand factor antigen (vWFAg), the ristocetin cofactor (FVIIIRiCof), euglobulin clot lysis time (ECLT), fibrinopeptide A (FPA), FPA generation time, activated partial thromboplastin time (APTT), vasopressin (aVP) and adrenaline.

3. During nausea plasma aVP concentrations rose from median values of 0.4 pg/ml (at time 0) to 76 pg/ml at peak nausea and fell to 32 pg/ml 20 min later. Adrenaline rose from 0.36 to 0.91 nmol/l (P < 0.05) before falling to 0.55 nmol/l.

4. During nausea, FVIIIC rose from 100% to 143% (P < 0.05) and to 214% (P < 0.05) 20 min later. FVIIIRiCof and vWFAg showed similar changes. Plasminogen activator activity (106/ECLT2) rose from 23 units at time 0 to 592 units during nausea and 1135 units (P < 0.05) after 20 min.

5. The APTT fell from 49 s to 44 s during the study, plasma FPA levels and the FPA generation time both remained unchanged.

6. On the four occasions nausea was not experienced, there were no changes in vasopressin and catecholamine concentrations nor in haemostatic function.

7. During the study, plasma aVP concentrations rose to levels previously shown to influence haemostatic function. This provides further support for the view that aVP has a secondary role as a mediator of acute changes in haemostasis, and during nausea contributes with adrenaline to an abrupt change in factor VIII and fibrinolytic activator activity.
Morphological and functional characteristics of isolated resistance vessels in advanced uraemia
Authors: Aalkjær C. , Pedersen E. B. , Danielsen H. , Fjeldborg O. , Jespersen B. , kjær T. , Sørensen S. S. , Mulvany M. J.
Published: August 2015

1. In order to obtain direct information on the properties of the resistance vasculature of patients with advanced uraemia, a technique was developed to dissect out small arteries (internal diameter about 165 μm) from biopsies of subcutaneous fat.

2. Such arteries responded in a concentration-dependent manner to noradrenaline and angiotensin II, and the maximal force developed suggested that the vessels were fully viable.

3. Although the biopsies were normally taken during operations under general anaesthesia, biopsies taken under local anaesthesia also appeared to be fully viable, suggesting that this technique may prove useful as a general method for studying the intrinsic vascular properties of humans.

4. Biopsies were taken from 20 patients with uraemia, all of whom were treated with chronic intermittent dialysis, and 11 control subjects; up to three vessels were examined per biopsy.

5. The uraemic state was not associated with changes in vascular morphology, or in vascular reactivity or sensitivity to noradrenaline, angiotensin II, potassium or calcium. However, for the uraemic patients and for the controls there was a positive correlation between mean blood pressure and the ratio of vessel media thickness to lumen diameter, as well as a negative correlation between mean blood pressure and vessel active media stress.

6. The results suggest that uraemia treated with dialysis may not be associated with altered properties of the resistance vasculature. However, it appears that uraemic hypertension is associated with both morphological and functional abnormalities of the resistance vasculature.
Muscle morphology and enzymes in proximal and distal muscle groups of lower limb from patients with corticosteroid treated rheumatoid arthritis: the relationship to maximal isokinetic muscle strength
Authors: Danneskiold-Samsøe B. , Grimby G.
Published: August 2015

1. Abnormal morphological and enzymatic patterns in the lateral vastus muscle have been found in women with corticosteroid treated rheumatoid arthritis. By means of biopsies from the lateral heads of right gastrocnemius muscles, the histology and enzyme activities were compared with those found in right vastus lateralis biopsies. The findings were correlated with isometric and isokinetic strength of the plantar flexors.

2. The relative occurrence of type I fibres in the gastrocnemius muscle was 46.4 ± 18.7 (sd) %, which is significantly higher than found in the vastus lateralis [35.7 ± 13.3 (sd) %] (P < 0.03).

3. The relatively lower percentage of type II fibres in the gastrocnemius muscle was due to a relatively low percentage of type II A fibres [mean 27.9 ± 16.4 (sd) %] (P < 0.05).

4. The area of type I fibres in the gastrocnemius muscle was 26.1 × 102 ± 10.0 (sd) μm2, which is 74% of the mean area for type I fibres found in the vastus lateralis (P < 0.01).

5. The area of type II fibres in the gastrocnemius was 14.9 × 102 ± 7.1 (sd) μm2, which is 77% of the mean area for type II fibres found in the vastus lateralis.

6. The isokinetic muscle strength of the plantar flexors in corticosteroid treated patients with rheumatoid arthritis was reduced to less than 50% at all angular velocities when compared with healthy women. The same difference was found in the knee extensors.

7. Both type I and type II fibre areas correlated positively with the activity of β-hydroxyacyl-CoA dehydrogenase (r = 0.72, P < 0.02; r = 0.77, P < 0.01). The activity of the oxidative enzyme citric acid synthase (but not β-hydroxyacyl-CoA dehydrogenase) correlated positively with the isokinetic muscle strength of the plantar flexors at all the angular velocities (r = 0.75, P < 0.01; r = 0.57, P < 0.05).

8. The isokinetic strength as well as the type I and II fibre areas in the vastus lateralis biopsies correlated well with the same parameters in the gastrocnemius muscle (r approx. 0.70, P < 0.001). The vastus lateralis and the gastrocnemius muscles had similar morphology in the same subjects. In the control subjects and in the patients a close correlation was found between the isokinetic strength of the knee extensors and the plantar flexors.

9. It is concluded that the corticosteroid effect on muscles seems to occur in both the proximal and distal skeletal muscles.
The influence of prednisone on the muscle morphology and muscle enzymes in patients with rheumatoid arthritis
Authors: Danneskiold-Samsøe B. , Grimby G.
Published: August 2015

1. Thirty-five female patients, mean age 63 years, suffering from rheumatoid arthritis participated the study. Twenty patients had been on long-term low-dose corticosteroid treatment. Fifteen patients had never received corticosteroids. A control group of 15 age- and sex-matched healthy subjects was also studied.

2. Examination of muscle biopsies from the (right) vastus lateralis and measurements of isokinetic and isometric knee-extension muscle strength were performed in all subjects.

3. Rheumatoid arthritis patients treated with corticosteroid showed a low percentage of type I fibres, mean 35.7 (range 17–66) % compared with patients who did not receive corticosteroid (P < 0.005). The latter group did not differ from the controls.

4. The muscle fibre areas also were affected in the corticosteroid treated rheumatoid patients. Type I and type II mean fibre areas were reduced by 32% and 50%, respectively, when compared with non-prednisone treated patients. The latter group did not differ from the controls in this respect.

5. A correlation was found between the isokinetic muscle strength of the knee extensors and the mean areas of type I and type II in patients treated with prednisone (r = 0.48, P < 0.05 and r = 0.58, P < 0.02 respectively). No such correlation was found when using isometric measurements of the knee extensors. A positive correlation was found in both groups of rheumatoid arthritis patients between the areas of the type I and type II fibres (r = 0.66–0.68, P < 0.05–0.02).

6. It is concluded that the observed abnormal muscle morphology and low knee-extension capacity found in the corticosteroid treated patients is due to the treatment rather than to other factors, as there were no other differences between the two groups of patients.
Intracellular acid-base and electrolyte metabolism in skeletal muscle of patients with chronic obstructive lung disease and acute respiratory failure
Authors: Fiaccadori E. , Del Canale S. , Arduini U. , Antonucci C. , Coffrini E. , Vitali P. , Meley R. , Guariglia A.
Published: August 2015

1. Quadriceps femoris muscle needle biopsies were performed in 21 patients with chronic obstructive lung disease (COLD) and acute respiratory failure (ARF) and in 21 age-matched healthy control subjects.

2. Muscle samples were analysed to obtain intracellular bicarbonate and pH values from total acid-labile carbon dioxide content. Muscle potassium, magnesium and sodium content were also determined, as well as water compartments.

3. Skeletal muscle of COLD patients with ARF showed intracellular acidosis and reduced potassium and magnesium content. Total muscle water increase was linked to extracellular water increment.

4. It was concluded that in COLD patients with ARF an overall derangement of skeletal muscle metabolism is present.
Non-esterified fatty acids may regulate human leucocyte sodium pump activity
Authors: Ng L. L. , Hockaday T. D. R.
Published: August 2015

1. Human leucocyte sodium pump activity was studied in normal fasting subjects by measuring the ouabain-sensitive 22Na+ efflux rate constants.

2. This 22Na+ efflux rate constant was inversely related to the fasting plasma non-esterified fatty acid level (rs = −0.73, P < 0.0001).

3. An oral glucose load (40 g/m2 surface area) led to an increase in the leucocyte ouabain-sensitive 22Na+ efflux rate constant after 2 h (1.97 ± 0.25 to 2.44 ± 0.19 h−1, P < 0.0001, n = 11). There was a concomitant fall in the plasma non-esterified fatty acid level.

4. Incubation of leucocytes in vitro with 100 μmol/l linoleic acid inhibited the leucocyte ouabain-sensitive 22Na+ efflux rate constant (1.52 ± 0.27 vs 0.84 ± 0.24 h−1, P < 0.001, n = 8).

5. The leucocyte Na+,K+-dependent adenosine triphosphatase (Na+,K+-ATPase) activity was inhibited in vitro by long chain non-esterified fatty acids, especially when unsaturated.

6. Non-esterified fatty acids may account for some of the Na+,K+-ATPase inhibitory activity of plasma.
Cerebrospinal fluid γ-aminobutyric acid levels in dogs with chronic portosystemic encephalopathy
Authors: Maddison J. E. , Yau D. , Stewart P. , Farrell G. C.
Published: August 2015

1. Cerebrospinal fluid (CSF) γ-aminobutyric acid (GABA) levels were measured in a dog model of spontaneous chronic portosystemic encephalopathy.

2. Dogs with congenital portacaval shunts (intra- or extra-hepatic) develop neurological features of abnormal psychomotor behaviour and depressed consciousness that are consistent with the symptoms of chronic portosystemic encephalopathy in humans. In the five dogs studied, plasma ammonia was elevated, as was CSF tryptophan, both usual biochemical abnormalities in portosystemic encephalopathy.

3. CSF levels of GABA in five dogs with portosystemic encephalopathy (100 ± 13 pmol/ml) were not significantly different from those in five control dogs (96 ± 14 pmol/ml). CSF levels of GABA were not altered after ammonia infusion.

4. If enhanced GABA-ergic neurotransmission, due to influx of gut-derived GABA into the brain, is responsible for the pathophysiology of chronic portosystemic encephalopathy in this model, it is not reflected by increased levels of GABA in CSF.