bluuebunny/crossref_metadata_2025 huggingface dataset:
Bile Salts, Hypotension and Obstructive Jaundice
Authors: Bomzon A. , Finberg J. P. M. , Tovbin D. , Naidu S. G. , Better O. S.
Published: August 2015

1. We have examined the effects of bile duct ligation on vascular and extravascular smooth muscle responsiveness to noradrenaline and tyramine using isolated rat hindlimb perfusion, and portal vein and vas deferens preparations.

2. Bile duct ligation reduced the contractile responses to noradrenaline of vascular and extra-vascular smooth muscle.

3. Exposure of smooth muscle to some bile salts caused a reduction in contractility.

4. This effect was dependent upon bile salt type and concentration.

5. These studies in vitro suggest that the reduced total peripheral resistance and hypotension seen in obstructive jaundice cannot be explained by a spasmolytic effect of some of the bile salts on smooth muscle.
Within-Breath Modulation of the Triggering of Extrasystoles in Man
Authors: Patrick J. M. , Gibson Zoë , Hanley S. P.
Published: August 2015

1. Sufficient isolated extrasystoles were recorded during a period of quiet breathing in nine patients to test the null hypothesis that there is no within-breath influence of respiration on the triggering of extrasystoles.

2. In five patients a highly significant respiratory modulation of the firing of extrasystoles was seen. The frequency distribution of extrasystoles during the respiratory cycle appeared to be approximately sinusoidal.

3. The phase relations varied with respiratory frequency, and the peak incidence occurred relatively later in the cycle when breaths were shorter: always at about 2 s after the start of inspiration.

4. An autonomic reflex mechanism, equivalent to that causing sinus arrhythmia, appears to be the most likely explanation.
Renal Excretion of Antidiuretic Hormone in Healthy Subjects and Patients with Renal Failure
Authors: Pruszczynski Wojciech , Caillens Henri , Drieu Luc , Moulonguet-Doleris Luc , Ardaillou Raymond
Published: August 2015

1. Urinary clearance of antidiuretic hormone (ADH) has been measured under basal conditions and during intravenous administration of arginine vasopressin in ten healthy subjects, and only under basal conditions in 18 patients with chronic renal failure and seven patients with acute renal failure at the polyuric phase of the disease.

2. In healthy subjects studied under conditions of mild water diuresis, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 3.3 ± 0.36 pg/ml, 25.2 ± 5.5 pg/min, 7.5 ± 1.2 ml/min and 6.4 ± 1.0% (means ± sem) respectively. When plasma ADH was raised to levels between 7 and 26 pg/ml during intravenous administration of the hormone, urinary excretion rate and urinary clearance of ADH increased. Tubular reabsorption of ADH did not reach a plateau but progressively increased in the range of plasma ADH studied.

3. In patients with chronic renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 2.8 ± 0.19 pg/ml, 9.4 ± 2.0 pg/min, 3.4 ± 0.6 ml/min and 10.0 ± 2.9% (means ± sem) respectively. Urinary excretion rate and urinary clearance were significantly lower than in healthy subjects.

4. In patients with acute renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 4.6 ± 0.47 pg/ml, 52.8 ± 15.8 pg/min, 9.5 ± 2.7 ml/min and 24.9 ± 4.4% (means ± sem) respectively. Urinary excretion rate and fractional clearance were higher than in healthy subjects and patients with chronic renal failure.

5. These results demonstrate that most of the filtered ADH is reabsorbed by the tubules. The reabsorptive capability is markedly diminished in patients with acute renal failure at the polyuric phase of the disease.
The Lipid-Lowering Effects of 3-Hydroxy-3-Methylglutaric Acid and Bile Acid Drainage in WHHL Rabbits
Authors: Van Niekerk J. L. M. , Hendriks Th. , Leuven J. A. Gevers , Havekes L. , De Boer H. H. M.
Published: August 2015

1. The effect of 3-hydroxy-3-methylglutaric acid (HMG) on serum cholesterol levels was investigated in Watanabe heritable hyperlipidaemic (WHHL) rabbits.

2. Oral administration of HMG resulted in a reduction of serum cholesterol by 39%.

3. Bile acid drainage, by means of either cholestyramine medication or partial ileal bypass (PIB) surgery, also led to significant reductions in circulating cholesterol, by 35 and 59% respectively.

4. Intraperitoneal injection of HMG after PIB surgery further reduced serum cholesterol by 35%.

5. Fibroblasts from the WHHL rabbits did not show high-affinity binding, uptake or degradation of 125I-labelled low density lipoprotein (LDL).

6. The working mechanism of these lipid-lowering therapies in WHHL rabbits is discussed in relation to recent literature.

7. The significant reductions in circulating cholesterol induced by HMG warrant further investigation into the use of this compound in the management of familial hypercholesterolaemia.
Histamine and Secretory Otitis Media
Authors: Collins M. P. , Bakhshi K. , Wareham C. A. , Church M. K.
Published: August 2015

1. Histamine, both free and cell associated, has been demonstrated in middle ear fluid from patients with secretory otitis media (SOM).

2. Histamine, mainly free in solution, has also been shown to be present in nasopharyngeal secretions taken from close to the Eustachian tube openings into the nasopharynx.

3. The adenoids from patients with middle ear effusion contained significantly (P<0.05) more histamine than those with no effusion.

4. However, in preliminary experiments, we could demonstrate no differences in the histamine secretory response of adenoids from SOM and non-SOM patients to anti-immunoglobulin E (anti-IgE), house dust mite antigen and calcium ionophore A23187 in vitro.

5. These results support the hypothesis of an inflammatory basis for SOM.
Assessment of Smoking Behaviour and Ventilation with Cigarettes of Differing Nicotine Yields
Authors: McBride Melanie J. , Guyatt Andrew R. , Kirkham Andrew J. T. , Cumming Gordon
Published: August 2015

1. Nine established cigarette smokers were each studied four times, smoking two identical cigarettes on each occasion. After an acclimatization study, they smoked one of three types of cigarettes, either their usual brand or one of two types of special low tar cigarettes. These latter both had tar yields of about 8 mg with nicotine yields of 0.55 (LN) and 0.90 (MN) mg respectively. The test order was randomized between individuals and before using the special cigarettes the subjects were given a pack to accustomize themselves.

2. While smoking each cigarette, magnetic tape recordings were made of puff rate, ventilation measured by respiratory inductive plethysmography (RIP) and nasal airflow measured with a modified oxygen cannula. The data were then processed digitally off-line.

3. Salivary nicotine and alveolar carbon monoxide levels were measured before and after smoking each cigarette, and the cigarette butt was analysed for nicotine.

4. While smoking behaviour varied considerably between the various subjects only small differences were seen between the different cigarette types in puff volume and duration and shape of the puff profile. Some changes in smoking behaviour occurred during the course of smoking a single cigarette.

5. Ventilatory patterns showed consistent inter-subject differences but there were no apparent variations due to the various cigarettes. Most subjects puffed during an expiration with the buccal cavity closed off, and then took a slower, deeper inspiration breathing through the mouth. Others, however, took puffs at any point in the respiratory cycle.

6. The different nicotine yields of the cigarettes produced marked changes in the butt and salivary nicotine measurements, but neither these, nor the changes in alveolar carbon monoxide, were closely related to ventilatory measurements. Possible explanations for these discrepancies are discussed.
Resistance to Methylprednisolone in Cultures of Blood Mononuclear Cells from Glucocorticoid-Resistant Asthmatic Patients
Authors: Poznansky Mark C. , Gordon Alastair C. H. , Douglas J. Graham , Krajewski Andrew S. , Wyllie Andrew H. , Grant Ian W. B.
Published: August 2015

1. In order to investigate the cellular mechanism of glucocorticoid resistance in chronic asthma, peripheral blood mononuclear cells (MNC) from asthmatic patients were cultured in soft agar.

2. Cells from patients known to be clinically sensitive to glucocorticoid therapy did not differ significantly from those of clinically resistant patients in terms of their immunophenotype or the number of colonies generated by culture in the presence of phytohaemagglutinin.

3. The glucocorticoid methylprednisolone (MP) at low concentration (10 nmol/l) inhibited colony growth from cells of glucocorticoid-sensitive patients, whereas there was much less inhibition of colony growth from resistant patients' cells.

4. In a small prospective study inhibition of colony growth by methylprednisolone in vitro correlated with the subsequently determined sensitivity of the patients' asthma to glucocorticoid therapy.

5. Assessment in vitro of glucocorticoid sensitivity may help to predict which patients may be spared ineffectual glucocorticoid medication. The results raise the possibility that peripheral blood mononuclear cells may respond to glucocorticoid in a similar manner to cells involved in the pathogenesis of asthma.
Effect of Sodium Loading on the Urinary Excretion of Prostaglandins E2 and F2α in Rats with Hereditary Diabetes Insipidus (Brattleboro Rats)
Authors: Rathaus M. , Kariv N. , Shapira J. , Bernheim J.
Published: August 2015

1. Current evidence suggests that the antidiuretic hormone (ADH) and changes in sodium balance influence renal prostaglandins (PGs). To separate these two mechanisms, the effect of sodium loading on the urinary excretion of PGE2 and PGF2α was studied in female Brattleboro rats with diabetes insipidus (DIHO) and compared with that in female, age matched, heterozygous Long Evans controls (LEHE).

2. Ten DIHO and ten LEHE rats had a normal sodium intake. In ten DIHO rats a 0.16% NaCl solution was supplied instead of drinking water for either 8 days (n = 5) or 14 days (n = 5). In two groups of LEHE rats, sodium loading was obtained with a 0.80% NaCl solution for the same study periods. Urine PGs were measured by radioimmunoassay in three 24 h urine collections for each rat.

3. Urine PGs were significantly increased in the 8 day loaded but not in the 14 day loaded LEHE rats. In DIHO rats, a non-significant increase in both PGE2 and PGF2α was present after 8 days of sodium loading, while PGE2 and the E/F ratio were decreased after 14 days of salt loading.

4. The findings suggest that the natriuresis induced by sodium loading in the rat may be mediated in part by increased production of PGs. In addition, it seems that ADH plays a role in this response.
Pharmacokinetics of Synthetic Human Parathyroid Hormone 1-34 in man Measured by Cytochemical Bioassay and Radioimmunoassay
Authors: Kent G. N. , Loveridge N. , Reeve J. , Zanelli Joan M.
Published: August 2015

1. Synthetic human parathyroid hormone (hPTH) 1-34 was given by intravenous injection to two healthy men. The time course of its appearance in and disappearance from the plasma was monitored both by cytochemical bioassay and by a specific radioimmunoassay (RIA) system.

2. Immunoreactive N-region parathyroid hormone (iPTH) reached peak concentrations in plasma at 2 min after injection, whereas peak concentrations of biologically active parathyroid hormone (bioPTH) were delayed until 4-6 min. Bioassayable PTH-like activity then disappeared from the plasma (mean transit times 5.8 and 8.6 min), approximately twice as fast as immuno-reactivity.

3. After separate subcutaneous administrations, a calculated 22-37% of administered hPTH 1-34 was subsequently detected in the plasma, by both assay systems.

4. It was not possible to explain fully the non-parallel appearances of bio- and immuno-reactivities in the plasma after intravenous injection nor the non-parallel disappearances after both intravenous and subcutaneous injections on the basis of the present data. It seems likely, however, that in the process of biological degradation the immunoreactive locus is inactivated by a different reaction from that which destroys bioactivity.

5. To investigate these activity dissociations further will require the application of microfractionation procedures in conjunction with both types of assay system.
Cardiovascular Properties of Metkephamid, a δ Opioid Receptor Agonist, in Man
Authors: Pasanisi Fabrizio , Sloan Lesley , Rubin Peter C.
Published: August 2015

1. Opioid receptors exist in at least three forms: μ, δ and κ. Agonists at μ receptors produce orthostatic hypotension in man by a mechanism involving a reduction in baroreflex sensitivity. We describe here the cardiovascular properties of metkephamid, a relatively selective δ opioid receptor agonist.

2. Blood pressure, heart rate and plasma noradrenaline concentration were measured over a 7 h period in eight normal young male volunteers in the supine position and after 70° 5 min head-up tilt, after receiving metkephamid (50 mg intramuscularly) or placebo.

3. Metkephamid increased heart rate in the supine position with no change in blood pressure or plasma noradrenaline concentration. This was accompanied by symptoms consistent with an anti-muscarinic anticholinergic effect.

4. Head-up tilt resulted in substantial hypotension after metkephamid with an attenuated change in heart rate and no increase in noradrenaline concentration.

5. We conclude that δ as well as μ opioid receptor agonists can produce orthostatic hypotension with attenuation of heart rate response. Metkephamid possesses anticholinergic properties not seen with μ receptor agonists, suggesting a possible role of δ opioid receptors in cholinergic activity.
Dopamine reduces aldosterone and 18-hydroxycorticosterone response to angiotensin II in patients with essential low-renin hypertension and idiopathic hyperaldosteronism
Authors: Witzgall Helmut , Lorenz Reinhard , Werder Klaus Von , Weber Peter C.
Published: August 2015

1. Plasma aldosterone, 18-hydroxycorticosterone (18-OH-B), 18-hydroxydeoxycorticosterone (18-OH-DOC), corticosterone, cortisol and prolactin levels were determined during an angiotensin II infusion at increasing rates both with and without a simultaneous infusion of dopamine in seven normotensive subjects, in ten patients with essential hypertension, and in ten patients with primary aldosteronism. In a second set of experiments, maximum increases of these plasma levels were determined after metoclopramide (10 mg intravenously) in all subgroups.

2. As compared with the other groups, an exaggerated angiotensin II-induced response of plasma aldosterone and 18-OH-B levels was observed in the five patients with low-renin essential hypertension (LREH) and in five patients with idiopathic hyperaldosteronism (IHA).

3. Dopamine reduced the maximal increase of aldosterone and of 18-OH-B after angiotensin II to 259 ± 48 (sem) pg/ml and 511 ± 152 pg/ml repectively in LREH (without dopamine: 515 ± 74 and 908 ± 201 respectively; P<0.05), and to 466 ± 197 and 741 ± 212 in IHA (without dopamine: 766 ± 193 and 1264 ± 337 respectively; P<0.05).

4. The maximal increases of plasma aldosterone, 18-OH-B, and prolactin after metoclopramide (10 mg intravenously) were higher (P<0.01) in patients with LREH and in patients with primary aldosteronism. Plasma levels of 18-OH-DOC, corticosterone and cortisol were not affected by the stimuli applied.

5. The exaggerated response to metoclopramide as well as to angiotensin II and its reversion only by pharmacological doses of dopamine are consistent with an increased but ineffective dopamine inhibition of aldosterone and 18-OH-B in LREH and IHA.
Is the urinary excretion of prostaglandin E in man dependent on urine pH?
Authors: Haylor J. , Toner J. M. , Jackson P. R. , Ramsay L. E. , Lote C. J.
Published: August 2015

1. The relationship between urine pH, modified by the oral administration of either ammonium chloride or sodium bicarbonate, and the urinary excretion of prostaglandin E (PGE) was studied in healthy female subjects.

2. The urinary concentration of PGE, normally constant in man, was significantly higher (P<0.02) in alkaline than in acid urine. pH-dependent metabolism and flow-dependent excretion were identified as two factors liable to obscure the demonstration of the pH-dependency of the urinary excretion rate of PGE in man.
The effect of acutely reduced plasma osmolality on acute renal failure in rats
Authors: Popovtzer Mordecai M. , Wald Hanna , Shilo Ruth
Published: August 2015

1. The present study was designed to evaluate the effect of acute fall in plasma osmolality in three models of acute tubular necrosis in rats: (a) glycerol, (b) arterial clamping and (c) mercuric chloride.

2. Plasma osmolality was reduced by a water loading during a mild anaesthesia from 305 ± 7 to 270 ± 12 mosmol/kg of water (P<0.01).

3. In the ischaemic models of acute tubular necrosis (glycerol and arterial clamping), during the first 24 h in rats with reduced plasma osmolality, the respective creatinine clearance rates (CCR), 0.04 ± 0.02 and 0.06 ± 0.04 ml/min, were strikingly lower than those in rats with normal osmolality, 0.21 ± 0.03 and 0.26 ± 0.06 ml/min (P<0.001) respectively. The control CCR were 0.65 ± 0.07 and 0.62 ± 0.07 ml/min respectively.

4. During the second day after induction of ischaemic (glycerol and arterial clamping) acute tubular necrosis, rats with reduced plasma osmolality exhibited a similar worsening in CCR as on the first day, when compared with that in rats with normal osmolality.

5. In rats with acute tubular necrosis induced with mercuric chloride reduction in plasma osmolality did not aggravate the severity of renal failure.

6. These results show that acute fall in plasma osmolality worsens the renal failure in the ischaemic but not in the nephrotoxic models of acute tubular necrosis.
Fibrinogen derivatives and platelet activation products in acute and chronic liver disease
Authors: Hughes R. D. , Lane D. A. , Ireland H. , Langley P. G. , Gimson A. E. S. , Williams Roger
Published: August 2015

1. The concentration in plasma of fibrinogen derivatives fibrinopeptide A (FPA) and Bβ1-42 and the platelet release products β-thromboglobulin (βTG) and platelet factor 4 (PF4) have been determined in patients with acute and chronic liver disease.

2. In 21 patients with fulminant hepatic failure on admission in grade III or IV coma the plasma FPA, Bβ1-42, βTG and PF4 levels were significantly increased compared with those in normal control subjects. On heparinization before haemoperfusion the FPA levels returned to the normal range and during resin and charcoal haemoperfusion there were no significant changes in the coagulation or platelet factors, except for a small increase in FPA with charcoal haemoperfusion.

3. In ten patients with compensated chronic liver disease there was a significant increase in Bβ1-42 and βTG levels but not FPA and PF4 as compared with normal controls.

4. Interpretation of the results is complicated by the possible reduced clearance of these proteins as a result of renal failure in some of the patients with fulminant hepatic failure and also by the damaged liver itself. However, these results have confirmed that disseminated intravascular coagulation can occur in both acute and chronic liver disease.
Scope and mechanisms of control of stimulus-secretion coupling in single varicosities of sympathetic nerves
Authors: Stjärne Lennart
Published: August 2015

Recent electrophysiological evidence from studies of sympathetic nerves in the guinea-pig vas deferens [1, 2] indicate that the transmitter content of a vesicle is the quantum secreted, that nerve impulses only intermittently evoke transmitter secretion from the average individual varicosity (P about 0.01) (cf. [3]), that transmitter secretion from a varicosity is monoquantal, and that release of both quanta of a ‘pair’ is followed by long secretory silence in that site. The sympathetic transmitter responsible for these effects is apparently not noradrenaline but adenosine 5'-trisphosphate (ATP) [4], presumably secreted as a co-transmitter with noradrenaline [4a, 4b]. If both transmitters are secreted in parallel, then on the evidence quoted above the maximal rate of secretion would be that at which every nerve impulse releases the noradrenaline contents of one vesicle from each varicosity. In the present study of the overflow of [3H]noradrenaline, selected pharmacological agents are used to examine this possibility. The results are interpreted in the light of the above-mentioned electrophysiological evidence, in an attempt to evaluate the scope and mechanisms of α-adrenoceptor-mediated control of stimulus-secretion coupling in the average individual varicosity of the sympathetic nerves of vas deferens.
α2-Adrenoceptors in dog kidney: autoradiographic localization and putative functions
Authors: Summers R. J. , Stephenson J. A. , Lipe S. , Neylon C. B.
Published: August 2015

1. The location of α2-adrenoceptors has been examined in slide-mounted sections of dog kidney by using labelling in vitro with [3H]rauwolscine and autoradiography.

2. [3H]Rauwolscine binding in dog kidney was of high affinity, saturable, and to a single population of sites. Stereoselectivity was observed for (−)-noradrenaline and the relative affinity of a series of competing antagonists indicated binding to α2-adrenoceptors.

3. Autoradiography of [3H]rauwolscine binding revealed localization to three areas: glomeruli, the intimal and adventitial surfaces of arcuate blood vessels and the medullary vascular bundles.
Prolonged Survival of Rat Renal Allografts after Multiple Allogeneic Pregnancies: Strain Specificity and role of Erythrocyte Antibody Rosette Inhibiting Antibodies
Authors: Asfar S. K. , Power D. A. , Mason R. J. , MacLeod A. M. , Simpson J. G. , Whiting P. H. , Engeset J. , Catto G. R. D.
Published: August 2015

1. The influence of allogeneic pregnancies on the survival of subsequent rat renal allografts was investigated in three rat strain combinations.

2. Multiple but not single pregnancies produced significantly more long-term surviving kidney grafts than were found in virgin animals; the effect was specific for paternal antigens, as multiple pregnancies by an unrelated strain did not prolong kidney graft survival.

3. In the multiparous groups, those animals with long-surviving grafts had significantly higher levels of non-cytotoxic antibodies against paternal strain B-lymphocytes (detected by the erythrocyte antibody rosette inhibition assay) than did animals which rejected their grafts.

4. The results show that multiple pregnancies may produce a state of specific unresponsiveness to paternal antigens, similar to enhancement, which is marked by the presence of non-cytotoxic antibodies against paternal B-lymphocytes. It is suggested, therefore, that enhancement may be one of the protective mechanisms which prevent rejection of the fetus during pregnancy.
Glomerular Sialic acid in Heymann Nephritis and Diacetylbenzidine induced Nephropathy in Rats
Authors: Laitinen Liisa , Miettinen Aaro , Tikkanen Ilkka , TÖrnroth Tom , Nordling Stig
Published: August 2015

1. Glomerular sialic acid was chemically measured in rats with experimental proteinuria induced by N,N'-diacetylbenzidine (DAB) or with autoimmune Heymann nephritis.

2. In DAB nephrosis and in Heymann nephritis the relative amount of glomerular protein was increased. In DAB nephrosis the quantity of sialic acid expressed per amount of protein was decreased, but expressed per amount of DNA, which reflects the number of cells, there was no significant change. In Heymann nephritis the amount of sialic acid was not significantly altered when expressed per amount of protein or per amount of DNA.

3. In individual animals, the amount of glomerular sialic acid expressed per amount of protein or per amount of DNA did not correlate with the severity of proteinuria. An increase in the total number of glomerular cells was found only in Heymann nephritis.

4. The results suggest that proteinuria in the reported models is not the result of changes in glomerular sialic acid.
Effect of Naloxone on the Defective Autonomic Control of Heart Rate in Uraemic Patients
Authors: Zoccali C. , Ciccarelli M. , Mallamaci F. , Maggiore Q.
Published: August 2015

1. The role of endogenous opioids on the reflex cardiovascular control of chronic uraemic patients was investigated.

2. The opiate antagonist naloxone administered intravenously caused a significant increase in the abnormal Valsalva manoeuvre ratio in nine chronic uraemic patients, but it had no effect in six diabetic patients with normal renal function, whose response to the Valsalva manoeuvre was similar to that of chronic uraemic patients. Naloxone had no effect in eight normal subjects.

3. The increase in the Valsalva ratio observed in uraemic patients was due to restoration of the parasympathetically mediated reflex bradycardia of the release phase of the manoeuvre.

4. Naloxone did not modify supine and standing blood pressure and heart rate in any group.

5. Endogenous opioids may be involved in the defective autonomic control of heart rate in uraemic patients.
An Association between Plasma Progesterone and Erythrocyte Carbonic Anhydrase in Women
Authors: Shepherd J.
Published: August 2015

I wish to bring attention to certain possible errors in the paper by J. Paciorek and N. Spencer (Clinical Science 1980, 58, 161-164) [1], where a correlation was found in women between erythrocyte carbonic anhydrase I concentration (RBC HCAI) and the progesterone peak during the menstrual cycle as well as a rise in RBC HCAI during pregnancy.
Early effects of ethinyloestradiol and norethisterone treatment in post-menopausal women on bone resorption and calcium regulating hormones
Authors: Selby Peter L. , Peacock Munro , Barkworth Stuart A. , Brown Wendy B. , Taylor Geoffrey A.
Published: August 2015

1. The early effects of sex steroid therapy were assessed in 28 normal post-menopausal women, 18 treated with ethinyloestradiol and 10 with norethisterone.

2. There was a reduction in the fasting urinary excretion of both calcium and hydroxyproline with both treatments, indicating reduced bone resorption. This was apparent after 1 week of therapy but became more marked after 3 weeks.

3. These changes were not accompanied by any changes in plasma levels of calcitonin or parathyroid hormone.

4. Patients receiving ethinyloestradiol showed a marked increase in plasma 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentration but this was explicable entirely in terms of increased plasma levels of vitamin D binding protein. There was no change in the free plasma level of 1,25(OH)2D. Patients treated with norethisterone showed no increase in plasma concentrations of 1,25(OH)2D.

5. We conclude that both ethinyloestradiol and norethisterone have a rapid and similar effect in reducing bone resorption. This is not mediated via the plasma levels of the calcium regulating hormones.
Changes in plasma volume, in transcapillary escape rate of albumin and in subcutaneous blood flow during hypoglycaemia in man
Authors: Hilsted J. , Bonde-Petersen F. , Madsbad S. , Parving H.-H. , Christensen N. J. , Adelhøj B. , Bigler D. , Sjøntoft E.
Published: August 2015

1. Hypoglycaemia was induced by insulin injected intravenously (0.15 i.u./kg body weight) in seven healthy young males.

2. Plasma volume was measured before and during hypoglycaemia by intravenous injection of 125I before hypoglycaemia and of 131I during hypoglycaemia. Plasma volume decreased and transcapillary escape rate increased significantly during hypoglycaemia.

3. Skin temperature and local subcutaneous adipose tissue blood flow were measured in four different regions. Both tended to decrease during hypoglycaemia and decreased significantly 2 h after hypoglycaemia. There was no correlation between changes in the two measurements, suggesting that there is no simple relationship between subcutaneous blood flow and skin temperature during hypoglycaemia.
Effects of atelectasis and vascular occlusion on the simultaneous measurement of serotonin and propranolol pulmonary extraction in dogs
Authors: Dargent Françloise , Gardaz Jean-Patrice , Morel Philippe , Suter Peter M. , Junod Alain F.
Published: August 2015

1. To test the relative sensitivity of serotonin and propranolol pulmonary extraction measurements to changes in pulmonary vascular surface, we sequentially subjected anaesthetized dogs to left upper lobe atelectasis, left lung atelectasis and left pulmonary artery occlusion.

2. We used a triple-indicator dilution technique to simultaneously measure the pulmonary extraction of serotonin and propranolol. After an initial series of measurements, dogs received dopamine and dextran to slightly increase pulmonary artery pressure and prevent further recruitment of capillaries.

3. Left upper lobe atelectasis did not modify the pulmonary extraction of serotonin and propranolol. Left lung atelectasis provoked a reduction in the serotonin extraction ratio by only 4%, whereas the propranolol extraction ratio decreased by 13%. After left pulmonary artery occlusion, propranolol and serotonin extraction ratios decreased by 16% and 5% respectively.

4. We conclude that the pulmonary extraction of propranolol is more sensitive to a decrease in pulmonary vascular surface than that of serotonin.
The effect of verapamil and inspired CO2 on the bronchoconstriction provoked by hyperventilation in normal humans
Authors: Twort C. H. C. , Neild J. E. , Cameron I. R.
Published: August 2015

1. Two groups of eight normal subjects were investigated in separate studies to demonstrate the effects of changes in end-tidal Pco2, and of pretreatment with the calcium antagonist drug verapamil, on bronchoconstriction provoked by voluntary hyperventilation.

2. Total respiratory resistance (Ros) was measured by the forced oscillation technique before and after 90s voluntary hyperventilation. End-tidal Pco2 during hyperventilation was varied by altering inspired CO2 concentration. When end-tidal Pco2 fell during hyperventilation, there was a rise in Ros. This did not occur if end-tidal Pco2 was controlled at a normal resting level during hyperventilation.

3. Specific conductance (sGaw) was measured before and after 90 s voluntary hyperventilation of air. Subjects were treated with oral verapamil or placebo for 2 1/2 days and the effect of hyperventilation on sGaw was reassessed. Verapamil reduced significantly the fall in sGaw caused by hyperventilation. Placebo had no effect.

4. In normal humans, bronchoconstriction provoked by hyperventilating air at ambient temperature and humidity is mediated by the fall in Pco2, and is also reduced by verapamil.
Enhancement of the sympathoadrenal response to the cold-pressor test by naloxone in man
Authors: Bouloux Pierre-Marc , Grossman Ashley , Al-Damluji Saad , Bailey Timothy , Besser Michael
Published: August 2015

1. The effects of naloxone (8 mg) on the pressor and plasma catecholamine response to a standard cold-pressor test have been evaluated in six normal male subjects. Plasma catecholamines were estimated by high performance liquid chromatography coupled to electrochemical detection.

2. Cold stimulation induced significant elevations in plasma noradrenaline and adrenaline to reach mean peak levels 61% and 108% above their respective basal levels (P < 0.05). Systolic blood pressure increased by 23 ± 6.5 mmHg (P < 0.001), and heart rate increased by 7.5 ± 2.5 beats/min (P < 0.001).

3. Naloxone pretreatment significantly enhanced the plasma adrenaline response to the cold stimulus by 98% (P < 0.01) with concomitant changes in peak systolic blood pressure (peak increment 31 ± 6 mmHg) and pulse rate (12.5 ± 3.5 beats/min) responses (both P < 0.05). The mean plasma noradrenaline response to cold also increased after naloxone, but this failed to achieve significance.

4. Endogenous opioids are likely to be involved in the sympathoadrenal response to a mild acute stress in man.
A technique for the measurement of orthophosphate in human erythrocytes, and some studies of its determinants
Authors: Challa A. , Bevington A. , Angier C. M. , Asbury A. J. , Preston C. J. , Russell R. G. G.
Published: August 2015

1. A technique is described for the determination of orthophosphate (Pi) in human erythrocytes. The advantages of the technique are that it uses whole blood rather than separated erythrocytes, that it avoids major hydrolysis of organic phosphates, that it takes account of incomplete recovery of Pi and that it minimizes the effects of chilling the cells.

2. In chilled samples from 46 patients in an intensive care unit, the cellular concentration of Pi was proportional to that in plasma.

3. Blood samples from nine normal subjects were incubated at 37°C. The cellular Pi was 0.79 mmol/litre of cells using an external standardization and 0.67 using an internal standardization. When the same cell samples were chilled on ice for 30 min, the internally standardized value decreased further to 0.57 mmol/litre of cells. These results suggest that differences in recovery, and the extent of chilling, contribute to the variability in the previously reported values for erythrocyte Pi.

4. If Pi, like chloride, had distributed passively between cells and plasma in these samples, the cell to plasma molar concentration ratio for Pi should have been 0.29, compared with the measured value of 0.64. This difference suggests that some factor, in addition to passive diffusion, determined the distribution of Pi.
Effect of chlorothiazide on serial measurements of exchangeable sodium and blood pressure in spontaneously hypertensive rats
Authors: Manhem P. J. O. , Clark S. A. , Brown W. B. , Murray G. D. , Robertson J. I. S.
Published: August 2015

1. Chlorothiazide (100 mg/kg body weight) was given by gavage daily to spontaneously hypertensive rats for 4 weeks. Another group of spontaneously hypertensive rats was given only tap water and served as control.

2. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment.

3. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats.

4. Chlorothiazide significantly attenuated the blood pressure increase in spontaneously hypertensive rats, the effect being most marked during the first 2 1/2 weeks of treatment and less thereafter.

5. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group.

6. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage.

7. When exchangeable sodium was expressed as mmol/rat, there was a more gradual rise in the chlorothiazide-treated animals, in accordance with their slower gain in weight.

8. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium.

9. Thus whereas chlorothiazide treatment of spontaneously hypertensive rats slows the increase of both weight and exchangeable sodium, other mechanisms are apparently responsible for the antihypertensive action of the drug.
Effect of 1,25-dihydroxyvitamin D deficiency on the metabolic clearance rate of 1,25-dihydroxyvitamin D3: studies using pigs with vitamin D-dependent rickets type 1
Authors: Fox John , Care Anthony D.
Published: August 2015

1. We have used pigs with inherited vitamin D-dependent rickets type 1 to study the effect of 1,25-dihydroxyvitamin D deficiency on the metabolic clearance rate of 3H-1,25-dihydroxyvitamin D3 infused to steady-state levels in plasma.

2. Plasma levels of 1,25-dihydroxyvitamin D were 24 ± 1 (sem) pmol/l in the hypocalcaemic, homozygous piglets and 196 ± 27 pmol/l in their normocalcaemic, heterozygous siblings.

3. The metabolic clearance rate of 1,25-dihydroxyvitamin D3 was the same in both normal heterozygous (0.90 ± 0.02) and hypocalcaemic, homozygous piglets (0.90±0.01 ml−1 min−1 kg−1 metabolic bodysize).

4. We conclude that a deficiency of circulating 1,25-dihydroxyvitamin D does not influence the clearance of 1,25-dihydroxyvitamin D3 from the circulation of pigs.
Left ventricular diastolic function of spontaneously hypertensive rats and its relationship to structural components of the left ventricle
Authors: Nishimura Hikaru , Kubo Shinichiro , Nishioka Akinori , Imamura Kikuko , Kawamura Keishiro , Hasegawa Motoharu
Published: August 2015

1. Left ventricular (LV) diastolic function was investigated in three different age groups (15, 28 and 50 weeks) of paired spontaneously hypertensive (SHR) and normotensive (WKY) rats under pentobarbital anaesthesia. A time constant of LV pressure decay, represented by T, was used as an index of LV relaxation. We assessed the relationship between haemodynamic parameters and LV structural components as quantified by microspectrophotometry (MSP), using multivariate analysis.

2. T was significantly prolonged in the 28 and 50 week old SHR compared with their normotensive counterparts (P < 0.05 and P < 0.01, respectively). T was prolonged by volume loading but was not affected with afterload elevation by angiotensin infusion in all age groups of the SHR and WKY.

3. LV wall thickness was greater in the SHR at all ages and was positively correlated with T (r = 0.42, P < 0.05).

4. A significant correlation was found between the increase in cardiac muscle fibre and collagen, the decrease in elastin and glycoprotein, and T on multivariate analysis (r = 0.53, P < 0.05).

5. We conclude that LV relaxation of SHR is disturbed from a relatively young age (28 weeks), for which we consider myocardial hypertrophy and LV structural changes found by MSP as being responsible.
A vasopressin-mediated diminution of potassium excretion in water-loaded man
Authors: Buckley J. , Gebruers E. M. , Hall W. J. , Harrington N. M. B.
Published: August 2015

1. Intravenous vasopressin (1–3 μ-units min−1 kg−1) had an antidiuretic effect on water-loaded man and also diminished potassium excretion. As noted by others, aspirin (2.4 g) enhanced the antidiuretic effect of vasopressin, but the fall in potassium excretion was not modified by prior administration of aspirin, which makes it unlikely that the fall was due to the release of endogenous prostaglandins.

2. After terminating the infusion of vasopressin, the fall in potassium output persisted longer than the antidiuresis, which makes it unlikely that the antikaliuretic effect of vasopressin is secondary to its effect on urine flow.

3. The unchanged antikaliuretic effect of vasopressin after aspirin treatment, together with its persistence after terminating the infusion, suggest the possible existence of vasopressin-mediated potassium absorption in the distal nephron in certain circumstances.

4. Aspirin administration had specific effects of its own in water-loaded man. It decreased both the water diuresis and sodium excretion but did not alter potassium excretion or urine osmolality.
Dietary fish oil prevents dexamethasone induced hypertension in the rat
Authors: Codde James P. , Beilin Lawrence J.
Published: August 2015

1. This study was designed to examine the effect of dexamethasone treatment on tissue and urinary prostanoids, and to determine whether inhibition of prostaglandin biosynthesis by manipulation of dietary fatty acids accelerates the development of glucocorticoid hypertension.

2. Forty-eight rats were placed on either a 2-series prostaglandin ‘inhibitory’ diet (cod liver oil/linseed oil) or a control diet of saturated fat for an initial period of 4 weeks. The groups were then divided into two so that half of each received dexamethasone in their drinking water (2.5 mg/1) for 1 week whilst continuing their respective dietary regimens.

3. Rats on the cod liver oil diet incorporated eicosapentaenoic acid into tissue stores with a corresponding decrease in arachidonic acid, and significantly impaired ability to generate serum thromboxane B2 (33%), aortic 6-oxo-prostaglandin F1α (44%), renal homogenate prostaglandin E2 (45%) and 6-oxo-prostaglandin F1α (74%) and urinary prostaglandin E2 (84%) and 6-oxo-prostaglandin F1α (79%).

4. Despite the diminished levels of vasodilator 2-series prostaglandins, the cod liver oil diet prevented the development of glucocorticoid induced hypertension.

5. Relative to their respective dietary controls, dexamethasone treatment resulted in decreased serum thromboxane B2 (20%) but increased aortic 6-oxo-prostaglandin F1α (186%), renal homogenate prostaglandins (127–230%) and urinary excretion of prostaglandin E2 (640–860%) and 6-oxo-prostaglandin F1α(230–365%) in both dietary groups.

6. It therefore seems unlikely that glucocorticoid induced hypertension is a consequence of inhibition of vasodilator prostaglandin synthesis.
Glutamine synthesis in the perfused rat kidney and in isolated rat cortical tubules: regulation by pH
Authors: Lanctin Henri , Brosnan John T. , Ross Brian D.
Published: August 2015

1. The possible involvement of renal glutamine synthesis in the regulation of ammoniagenesis during metabolic acidosis has been investigated.

2. Using an isotope dilution technique glutamine synthesis has been demonstrated in the intact perfused rat kidney, despite zero net balance for glutamine in this preparation.

3. Inhibition of glutamine synthesis resulted in increased ammonia production in isolated cortical tubules. The rates of these processes were comparable.

4. We conclude that recycling of nitrogen through glutamine synthesis and glutamine hydrolysis could play a quantitatively significant role in the control of ammonia excretion by the kidney, particularly in acute acidosis where the fall in pH seems to inhibit glutamine synthesis.
Cardiac metabolism and performance during l-glutamic acid infusion in postoperative cardiac failure
Authors: Pisarenko O. I. , Lepilin M. G. , Ivanov V. E.
Published: August 2015

1. Intravenous infusion of l-glutamic acid results in the augmentation of the cardiac output and an improvement of the circulation in patients with postoperative cardiac failure. This effect is not accompanied by increased myocardial oxygen demand.

2. Arterial plasma glutamate level rises 10-fold and arterial-coronary sinus plasma glutamate difference increases fivefold during intravenous l-glutamic acid infusion. This leads to cessation of ammonia release from the myocardium, probably due to augmentation of glutamine synthesis and to an increase in alanine formation coupled with a change from lactate release to lactate uptake by the myocardium.

3. The data obtained suggest that the beneficial effect of l-glutamic acid on depressed cardiac function in postoperative patients is related to changes in myocardial metabolism. Glutamic acid may be useful in treatment of circulatory and metabolic disturbances in cardiac failure.
Borderline maintenance of erythrocyte 2,3-diphosphoglycerate concentrations in normoxic type 1 (insulin dependent) diabetic subjects
Authors: Story C. J. , Roberts A. P. , Ryall R. G.
Published: August 2015

1. Erythrocyte 2,3-diphosphoglycerate and haemoglobin A1C concentrations were measured in 26 clinically normoxic patients with type 1 (insulin dependent) diabetes mellitus. The concentration of 2,3-diphosphoglycerate theoretically required to maintain normal erythrocyte oxygen delivery function in each subject was calculated and compared with the measured concentrations.

2. In the majority of diabetic patients 2,3-diphosphoglycerate concentrations were sufficient to keep the erythrocyte oxygen dissociation curve within the normal range under otherwise normal blood conditions. There was, however, a minority of patients in which this was not true.

3. It is concluded that the increased erythrocyte 2,3-diphosphoglycerate concentrations in clinically normoxic diabetic subjects are generally less than compensatory for the effect of haemoglobin A1C formation on the haemoglobin-oxygen dissociation curve.
Contribution of Vasopressin to the maintenance of blood pressure in deoxycorticosterone-salt induced malignant hypertension in spontaneously hypertensive rats
Authors: Hiwatari Masao , Abrahams Josephine M. , Saito Takao , Johnston Colin I.
Published: August 2015

1. In the present study, deoxycorticosterone (DOC) and salt was administered to Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) by using silicone-rubber implants (DOC acetate, 100 mg/kg) and 0.9% NaCl as drinking water. SHR treated with DOC-salt for 4 weeks showed the characteristics of malignant hypertension including marked increases in blood pressure and left ventricular weight with typical histological changes in the kidney.

2. DOC-salt treatment increased plasma vasopressin levels in WKY (from 6.1 ± 0.5 to 8.9 ± 0.8 pmol/l) but significantly more in SHR (from 5.0 ± 0.6 to 15.8 ±1.2 pmol/l).

3. Intravenous administration of the specific antagonist to the pressor effect of vasopressin, d(CH2)5Tyr(Me)AVP (10μg/kg), decreased mean arterial pressure of DOC-salt treated WKY and SHR by 6.6 ± 0.9mmHg (P < 0.05) and 9.7 ± 1.7 mmHg (P < 0.05) respectively.

4. DOC-water treatment also increased plasma AVP levels in SHR to 10.5 ± 0.8 pmol/l, but the vasopressin antagonist had little effect on blood pressure in these rats.

5. Plasma levels of vasopressin were significantly correlated with both mean arterial pressure (r = 0.64) and left ventricular weight (r = 0.74). This suggests a close relationship between plasma AVP and severity of hypertension.

6. The results of the present experiment demonstrate that vasopressin is part of the overall pressor mechanism which contributes to the maintenance of blood pressure in DOC-salt induced malignant hypertension in SHR, but the small fall in pressure produced by the AVP antagonists suggests that the contribution is of only minor importance.
Vasopressin, aldosterone and renin responses to volume depletion in heart-transplant recipients
Authors: Drieu Luc , Rainfray Muriel , Cabrol Christian , Ardaillou Raymond
Published: August 2015

1. Plasma arginine vasopressin (AVP), renin activity (PRA) and aldosterone (ALD) were measured immediately before and 60 min after intravenous administration of frusemide and passage from lying to standing in 10 untreated healthy subjects (group 1), eight asthmatic patients treated with prednisone (group 2) and 13 heart-transplant recipients treated with prednisone and cyclosporine (group 3). Three different tests for cardiac vagal innervation were performed in the study population. They confirmed that the patients of group 3 were denervated whereas those of groups 1 and 2 had an intact cardiac innervation.

2. Plasma volume depletion after frusemide administration estimated from the rise in plasma proteins was 10–12%. Mean blood pressure was higher in the transplant recipients but did not change in the three groups. Heart rate was also greater in the transplant recipients as a result of vagal denervation. PRA and ALD increased in all the subjects: 2.8, 3.3 and 2.2 times basal value for PRA, 2.7, 4.6 and 2.1 times basal value for ALD in groups 1, 2 and 3 respectively. In contrast, plasma AVP increased only in the two control groups (× 1.45 and × 1.65 in groups 1 and 2 respectively) whereas it was unchanged in the group of heart-transplant recipients (× 1.05).

3. In order to better understand the etiology of the high basal AVP plasma levels observed in group 3, AVP response to a standard water load was studied in eight supplementary heart-transplant recipients: 81.5% of the water load was excreted over 3 h and plasma AVP fell significantly (× 0.76).

4. These results suggest that, in humans, cardiac receptors and innervation play a dominant role in AVP response to volume depletion. In contrast, we found no evidence for a dominant role of cardiac receptors and innervation in mediating renin and aldosterone secretion.