bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Uninephrectomy on Urinary Prostaglandin E2, F2α, and 6-Ketoprostaglandin F1α Excretion in Rats
Authors: Baer Philip G. , Nasjletti Alberto
Published: August 2015

1. Male Wistar rats were used to examine whether renal prostaglandins (PG) contribute to functional compensatory changes in the remaining kidney after uninephrectomy. Total urinary excretion of PGE2, PGF2α and 6-keto-PGF1α, a metabolite of PGI2, was measured before and during 11 days after surgery in uninephrectomized (UNX, n = 8) and sham-operated control (S, n = 9) rats.

2. Urine volume was increased for the UNX rats on days 2–8 after surgery, but not thereafter, and urine osmolality for UNX was decreased on post-surgery days 1–9; total urinary sodium excretion did not differ between the two groups. Urinary PGE2 excretion was decreased in the UNX rats to 50% of S rat values, except on post-surgery days 2 and 3, when values for the two groups were not significantly different. Urinary PGF2α excretion by the UNX rats was reduced to 50% of S rat values throughout the post-surgery period. In contrast, the urinary excretion of 6-keto-PG1α by the UNX rats did not differ significantly from that by the S rats, except on a single day.

3. Chronic renal functional adaptation to renal mass reduction does not depend on increased renal prostaglandin systems activity; however, increased intrarenal PGE2 activity in the remaining kidney might be a factor in compensatory adjustments during the first days after surgery.
Calmodulin Distribution and Ca2+ Transport in the Erythrocytes of Patients with Essential Hypertension
Authors: Postnov Yu. V. , Orlov S. N. , Reznikova M. B. , Rjazhsky G. G. , Pokudin N. I.
Published: August 2015

1. The rate of calcium transport and calmodulin distribution in the erythrocytes of patients with essential hypertension were studied. In erythrocyte membranes subjected to calmodulin depletion by treatment with EGTA, both the affinity of the calcium pump for Ca2+ and its maximal activity were the same in normotensive and hypertensive patients.

2. The addition of exogenous calmodulin to calmodulin-stripped membranes from erythrocytes of patients with essential hypertension resulted in a smaller increase of the maximal activity of the calcium pump and its affinity for Ca2+. The addition of calmodulin to erythrocyte membranes obtained without EGTA treatment resulted in a smaller increase of the maximal activity of the calcium pump only.

3. There were no significant differences of calmodulin distribution (cytoplasmic concentration and size of the membrane-bound pool) between the erythrocytes of normotensive and hypertensive patients.

4. It is suggested that alterations in the calcium pump activity of the erythrocyte membranes of patients with essential hypertension are related to the alteration of interaction between calmodulin and Mg2+, Ca2+-ATPase.
The Immediate Pressor Response to Saralasin in Man: Evidence against Sympathetic Activation and for Intrinsic Angiotensin II-Like Myotropism
Authors: Mathias C. J. , Unwin R. J. , Pike F. A. , Frankel H. L. , Sever P. S. , Peart W. S.
Published: August 2015

1. The cardiovascular and hormonal effects of intravenous saralasin (0.5, 1 and 5 μg min−1 kg−1) were assessed in nine tetraplegic patients (with complete cervical spinal cord transaction above the sympathetic outflow) and in six normal subjects.

2. In the tetraplegic patients, saralasin caused an immediate transient pressor response which was not dose-dependent and substantially greater than the pressor response in normal subjects. The pressor response in the tetraplegic patients was not accompanied by a rise in levels of plasma noradrenaline.

3. In the tetraplegic patients, after α-adrenoceptor blockade with thymoxamine (1 mg kg−1 h−1), twice the dose of intravenous noradrenaline was needed to induce the same pressor response. The pressor response to saralasin (5 μg kg−1 min−1), however, was unaffected by thymoxamine.

4. Saralasin caused minimal changes in levels of plasma renin activity and plasma aldosterone in both groups. There was no relationship between basal plasma renin activity and the pressor response in either group.

5. We therefore conclude that the immediate transient pressor response to saralasin in man is not due to central sympathetic stimulation, is unlikely to be due to peripheral sympathetic activation and is probably the result of intrinsic angiotensin II-like myotropism.
Oxalate Dynamics and Removal Rates during Haemodialysis and Peritoneal Dialysis in Patients with Primary Hyperoxaluria and Severe Renal Failure
Authors: Watts R. W. E. , Veall N. , Purkiss P.
Published: August 2015

1. We have measured the plasma oxalate concentration (POx), urinary oxalate excretion (UOx), oxalate equilibrium distribution volume (ODV), oxalate metabolic pool size [(ODV) × (POx)], total plasma oxalate clearance (PCOx), renal (or dialyser) oxalate clearance (RCOx), non-renal oxalate clearance (NRCOx) and the tissue oxalate accretion rate (TOA)= [(NRCOx) × (POx)] in three patients with severe renal failure due to primary hyperoxaluria who were being treated by peritoneal dialysis or haemodialysis, or by renal transplantation. The clearance (either GFR or dialyser) of [99mTc]diethylenetriaminepenta-acetate (DTPA) and the extracellular fluid volume (ECF) measured as [99mTc]DTPA distribution volume were also determined.

2. Negligible amounts of 14C were found in faeces or as 14CO2 in expired air and hence (NRCOx) = (PCOx-RCOx).

3. Haemodialysis removed oxalate more efficiently than peritoneal dialysis in the patient where a direct comparison was possible. Neither treatment could keep up with the TOA when performed for clinically acceptable times.

4. The plasma oxalate concentrations calculated from 14C clearance through the dialyser and the chemically determined concentration of the oxalate in the dialysate were in the range 111–146 μmol/l. This is higher than in normals and in hyperoxaluric patients who are not in renal failure. Hence, although the ODV and ECF are similar to those of hyperoxaluric patients without renal failure and normal control subjects, the oxalate metabolic pool (ODV × POx) is grossly enlarged.

5. In the patient treated by renal transplantation, the oxalate pool size diminished concurrently with the resumption of oxalate excretion but expanded again as renal function decreased due to oxalosis.

6. The quantitative data show that dialysis procedures can only be a temporary holding operation and the prognosis with transplantation remains bad unless excessive oxalate production can be controlled.
Simultaneous Measurement of Renal Clearance and Plasma Clearance of 99mTc-Labelled Diethylenetriaminepenta-Acetate, 51Cr-Labelled Ethylenediaminetetra-Acetate and Inulin in Man
Authors: Rehling M. , Møller M. L. , Thamdrup B. , Lund J. O. , Trap-Jensen J.
Published: August 2015

1. The present investigation was undertaken to study the kinetics of 99mTc-labelled diethylene-triaminepenta-acetate (DTPA) as compared with inulin and 51Cr-labelled ethylenediaminetetra-acetate (EDTA).

2. Twenty patients with various degrees of decreased renal function were studied. The renal clearance, plasma clearance and volume of distribution of all three tracers were measured after a simultaneous single injection.

3. The average renal clearance ratio 99mTc-DTPA to inulin was 0.97; the average renal clearance ratio 99mTc-DTPA to 51Cr-EDTA was 1.02.

4. In all patients the plasma clearance of inulin exceeded that of 99mTc-DTPA. No difference was seen between the plasma clearance of 99mTc-DTPA and 51Cr-EDTA. The plasma clearance of all three tracers overestimated the simultaneously measured renal clearance; on average this was, for 99mTc-DTPA 5.7 ml/min, for 51Cr-EDTA 6.0 ml/min and for inulin 8.1 ml/min. The plasma clearance of 99mTc-DTPA correlated well with the renal clearance of inulin, but overestimated this by 3.5 ml/min on average.

5. The volume of distribution of inulin was less than that of 99mTc-DTPA and 51Cr-EDTA. No difference was seen between the volume of distribution of 99mTc-DTPA and 51Cr-EDTA.

6. It is concluded that the difference in the kinetics of 99mTc-DTPA and 51Cr-EDTA in patients with decreased renal function was small and without clinical relevance. The two radio-actively labelled tracers can replace each other in assessment of glomerular filtration rate (GFR). The close correlation between the plasma clearance of 99mTc-DTPA after a bolus injection and the renal clearance of inulin justifies the use of the single-injection technique in assessment of GFR.
The relative proportions of fat, muscle and bone in the normal human forearm as determined by computed tomography
Authors: Maughan R. J. , Watson J. S. , Weir J.
Published: August 2015

1. Computed tomography has been used to establish the proportions of fat, muscle and bone present in the normal human forearm.

2. Subjects were healthy young volunteers, eight males and eight females. A series of six cross-sectional scans at right angles to the long axis of the forearm was obtained, the scans being made at equidistant intervals between the olecranon process and the ulnar styloid.

3. The volumes occupied by fat, muscle and bone were calculated for the complete forearm. Total forearm volume calculated by this method agreed closely with that measured by water displacement.

4. For the male subjects, forearm composition was 72.1 ± 4.4% muscle (mean ± SD), 15.0 ± 5.3% fat and 12.9 ± 1.2% bone. Female forearms had less muscle (P<0.001) and more fat (P<0.001) than those of the male subjects: 58.5 ± 4.0% muscle, 29.3 ± 5.0% fat and 12.3 ± 1.4% bone.

5. Forearm muscle volume was significantly correlated (r= 0.75; P<0.05) with lean body mass in the male subjects; the range of values for lean body mass in the female subjects was too small to permit calculation of the equivalent relationship.

6. Forearm fat content, as a percentage of total volume, was proportional to whole body fat content as estimated from skinfold thickness (males, r = 0.84; P< 0.01; females, r = 0.77; P< 0.05).
Oxalate Absorption and Postprandial Urine Supersaturation in An Experimental Human Model of Absorptive Hypercalciuria
Authors: Erickson Stephen B. , Cooper Kerry , Broadus Arthur E. , Smith Lynwood H. , Werness Peter G. , Binder Henry J. , Dobbins John W.
Published: August 2015

1. The effect of 1,25-dihydroxyvitamin D [1,25-(OH)2D] on dietary oxalate absorption and postprandial urine supersaturation with calcium oxalate was determined in 11 normal subjects.

2. 1,25-(OH)2D increased the urinary excretion of orally administered [14C]oxalate in the 8 h period after a liquid meal containing 1.875 mmol of calcium and 0.83 mmol of oxalate (P < 0.01), and during a 48 h period when the subjects ingested a diet containing 25 mmol of calcium and 3.3 mmol of oxalate/day (P < 0.01); however, 1,25-(OH)2D administration had no effect on [14C]oxalate excretion when calcium was removed from the liquid meal.

3. 1,25-(OH)2D increased 24 h urinary oxalate excretion from 28.7 ± 2.1 mmol/mol of creatinine to 36.8 ± 2.6 mmol/mol of creatinine (P < 0.05) on the 10 mmol/day calcium diet and from 26.4 ± 2.9 to 33.2 ± 2.2 mmol/mol of creatinine (P < 0.1) on the 25 mmol/day calcium diet.

4. A linear correlation (r = 0.72) was found between plasma 1,25-(OH)2D levels and urinary [14C]oxalate excretion after the liquid meal.

5. 1,25-(OH)2D administration produced postprandial supersaturation of urine with calcium oxalate and calcium oxalate crystalluria.

6. These studies suggest that 1,25-(OH)2D increases oxalate absorption (and urinary excretion) by increasing calcium absorption, which results in less binding of calcium to oxalate in the intestine; therefore more oxalate is available for absorption. The combined effect of increased calcium and oxalate absorption results in postprandial supersaturation of urine with calcium oxalate, with resultant crystalluria.
The time Course During 36 Weeks’ Endurance Training of Changes in o2 max. and Anaerobic Threshold as Determined with a new Computerized Method
Authors: Smith D. A. , O'Donnell T. V.
Published: August 2015

1. Six healthy male subjects followed a programme of endurance training for 36 weeks. At 12 week intervals each underwent an incremental exercise test to maximum on a treadmill. Minute ventilation, cardiac frequency, expired and end-tidal concentrations of oxygen and carbon dioxide, oxygen uptake and carbon dioxide output were measured continuously during each test.

2. Anaerobic threshold (AT) was determined non-invasively as the onset of sustained increases in each of the ventilatory equivalent for oxygen, expired and end-tidal concentrations of oxygen followed by an increase in ventilatory equivalent for carbon dioxide after a brief delay due to isocapnic buffering. A new computerized cumulative-sum method was employed.

3. Significant increases in maximum oxygen uptake (Vo2 max.) of 13.6%, AT (32.3%) and % AT/Vo2 max. (17.0%) and a significant decrease (10.2%) in cardiac frequency at an oxygen uptake of 1.0 litres/min (fc1.0) were observed at the completion of the training programme.

4. The time courses of the changes for each of AT, Vo2 max. and fc1.0 were not identical during the training. Compared with Vo2 max. the disproportionate increases in AT occurred earlier and were usually completed within 12 weeks. Vo2 max. increased for the first 24 weeks of training, but showed no further increase over the final 12 weeks. fc1.0 decreased through the whole training period.

5. The improved AT after training is more likely to be related to improved peripheral utilization of oxygen than to an improved oxygen delivery to muscles.
The Role of Opioid Peptides in the Hormonal Responses to Acute Exercise in Man
Authors: Grossman A. , Bouloux P. , Price P. , Drury P. L. , Lam K. S. L. , Turner T. , Thomas J. , Besser G. M. , Sutton J.
Published: August 2015

1. Opioid involvement in the physiological and hormonal responses to acute exercise was investigated in six normal male subjects. Each was exercised to 40% (mild exercise) and 80% (severe exercise) of his previously determined maximal oxygen consumption on two occasions, with and without an infusion of high-dose naloxone. The exercise task was a bicycle ergometer; mild and severe exercise were performed for 20 min each, followed by a recovery period.

2. Exercise produced the expected increases in heart rate, blood pressure, ventilation, tidal volume, respiratory rate, oxygen consumption and carbon dioxide production. After severe exercise, naloxone infusion increased ventilation from 94.8 ± 4.9 litres/min to 105.7 ± 5.0 litres/min (P<0.05), but had no effect on any of the other physiological variables.

3. Exercise-induced changes in several hormones and metabolites were noted, including elevations in circulating lactate, growth hormone (GH), prolactin, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenaline, noradrenaline, plasma renin activity (PRA) and aldosterone. There was no change in plasma met-enkephalin. Naloxone infusion produced the expected increases in LH and cortisol, but also significantly enhanced the elevations in prolactin, adrenaline, noradrenaline, plasma renin activity and aldosterone (P<0.05).

4. Psychological questionnaires revealed minor mood changes after exercise, but no evidence was found for the suggested ‘high’ or euphoria of exercise. Effort was perceived as greater during the naloxone infusion than the saline infusion in every subject.

5. We conclude that endogenous opioids may be important in the control of ventilation and the perception of effort at high levels of power output, and may modulate the responses of circulating catecholamines and the renin-aldosterone system to acute physical stress.
Near-Normal Glycaemic Control Does not Correct Abnormal Platelet Reactivity in Diabetes Mellitus
Authors: Jackson C. A. , Greaves M. , Boulton A. J. M. , Ward J. D. , Preston F. E.
Published: August 2015

1. The effect of improved glycaemic control, effected by 16 weeks continuous subcutaneous insulin infusion (CSII), on platelet aggregation and platelet prostaglandin biosynthesis has been assessed in a group of 11 diabetic patients with painful peripheral neuropathy.

2. Before CSII and compared with results obtained on samples from age- and sex-matched control subjects, there was enhanced reactivity of the platelets from diabetic patients to ADP, collagen and sodium arachidonate (NaAA). There was also increased thromboxane B2 (TXB2) production after platelet stimulation by NaAA. In contrast, collagen-induced thromboxane production by platelets from diabetic patients was significantly less than that of platelets from controls.

3. Treatment by CSII resulted in a statistically significant improvement in glycaemic control and this was maintained for the 16 week period of the study. At 16 weeks and in the presence of near-normal glycaemic control, the enhanced platelet reactivity in response to collagen and NaAA persisted and that to ADP was further increased. Collagen-induced thromboxane production was, however, corrected by CSII.
Effect of Small Increments in Plasma Calcium Concentration on the Responsiveness of Forearm Resistance Vessels to Verapamil in Normal Subjects
Authors: Robinson B. F. , Phillips R. J. W.
Published: August 2015

1. The effect of a small increase in local plasma calcium concentration on the responsiveness of the forearm resistance vessels to verapamil has been examined in normal subjects, by using a plethysmographic method with infusion of calcium and other agents into the brachial artery.

2. Infusion of calcium at a rate which increased the concentration in forearm venous blood by about 0.5 mmol/l caused basal blood flow to fall by 19% and the dilator response to verapamil to fall by 35% (n = 8; P<0.02).

3. When, after 46 min, the infusion of calcium was discontinued, the dilator response to verapamil increased to reach a level 53% higher than the initial control (n = 8; P<0.02).

4. Infusion of calcium had no effect on the dilator response to sodium nitroprusside.

5. Infusion of noradrenaline at a rate which caused a greater reduction in basal flow than that induced by calcium had no effect on the response to verapamil.

6. It is concluded that the dilator response to verapamil, which is thought to reflect activity of the potential operated system for calcium entry, is selectively depressed by a small elevation of plasma calcium concentration, but subsequently becomes elevated. These findings point to an important role for calcium in the regulation of membrane function in the resistance vessels and support the view that altered calcium handling may contribute to the development of primary hypertension.
Effects of Acipimox, a Nicotinic Acid Derivative, on Lipolysis in Human Adipose Tissue and on Cholesterol Synthesis in Human Jejunal Mucosa
Authors: Stirling C. , McAleer M. , Reckless J. P. D. , Campbell R. R. , Mundy D. , Betteridge D. J. , Foster K.
Published: August 2015

1. The mode of action of acipimox (5-methyl-pyrazine carboxylic acid 4-oxide), an hypotriglyceridaemic agent, was examined in human adipose tissue and intestinal mucosa.

2. The rates of release of fatty acids and glycerol from human adipose tissue were measured in vitro. The release of fatty acids and glycerol from adipose tissue maximally stimulated by isoprenaline (10−5 mol/l) fell by 40 and 25% respectively (P<0.025 and P<0.025) in the presence of acipimox (10−5 mol/l). In submaximally stimulated adipose tissue (isoprenaline 10−7 mol/l) acipimox (10−4 mol/l) fully inhibited release of fatty acids (P<0.05) and glycerol (P<0.025) to basal rates. In unstimulated adipose tissue acipimox (10−3 mol/l) reduced the rate of glycerol release (P<0.05), but not the rate of fatty acid release.

3. Cholesterol synthesis in jejunal mucosa was measured in vitro by the incorporation of [2-14C]-acetate into sterols. Addition of cholesterol to the incubation reduced [2-14C]acetate incorporation into sterols from 8.7 ± 2.1 (mean ± standard error) to 3.7 ± 1.0 pmol h−1 mg−1 of tissue (P<0.01). Acipimox at 10−4-10−2 mmol/l had no consistent effect on cholesterol synthesis.

4. Acipimox appears to exert its main hypolipidaemic effect by reducing lipolysis and free fatty acid flux to the liver, thereby reducing the precursor pool size of very low density lipoprotein (VLDL)-triglyceride and VLDL synthesis.
Frusemide-Sensitive Sodium and Potassium Transport by Human Leucocytes
Authors: Johnson Valerie E. , Hilton P. J.
Published: August 2015

1. Frusemide-sensitive sodium and potassium transport by normal human leucocytes has been studied in vitro by both isotopic and net flux techniques.

2. In physiological media the leucocyte exhibits a frusemide-sensitive influx of sodium and potassium of equal magnitude compatible with a 1:1 co-transport system.

3. Cells exposed to zero external sodium and potassium (osmolality maintained with choline) demonstrated a frusemide-sensitive sodium and potassium efflux.

4. Frusemide-sensitive potassium influx was dependent on the presence of external sodium but frusemide-sensitive sodium influx persisted unchanged in the absence of external potassium.

5. Frusemide-sensitive potassium influx was dependent on external chloride but frusemide-sensitive sodium influx was chloride-independent.

6. These last two observations make it likely that the frusemide-sensitive pathway is capable of operating in modes other than sodium-potassium co-transport.
Mast Cell-Dependent Inflammatory Mediators and their Putative Role in Bronchial Asthma
Authors: Robinson C. , Holgate S. T.
Published: August 2015

Introduction: Bronchial asthma is a disease of complex aetiology characterized by both pathological and physiological abnormalities which lead to widespread but reversible airways obstruction. Pathologically, the airways exhibit evidence of mucosal oedema, damage to the respiratory bronchial epithelium and infiltration with large numbers of eosinophils, neutrophils and mononuclear cells [1, 2]. One of the cardinal features of asthma is an increased reactivity of the airways to specific and nonspecific bronchial provocation. Whilst the reasons for this increased airway reactivity have not yet been defined, there is evidence that many of the pathophysiological changes in asthma, which are tantamount to an inflammatory response, may be accounted for by the actions of released chemical mediators [3, 4]. This article reviews some of the recent advances made in this area, with particular emphasis on the likely roles of those mast cell-dependent mediators which are generated de novo after cell activation.
Cytoplasmic Free [Ca2+] is Increased in the Platelets of Spontaneously Hypertensive Rats and Essential Hypertensive Patients
Authors: Bruschi Giacomo , Bruschi Maria E. , Caroppo Maurizio , Orlandini Guido , Spaggiari Marco , Cavatorta Angelo
Published: August 2015

1. The cytoplasmic free calcium concentration ([Ca2+]i) was assessed with the fluorescent dye Quin 2 in platelets and lymphocytes of spontaneously hypertensive rats (SHR), normotensive Wistar—Kyoto rats (WKY), essential hypertensive patients (EHP) and normotensive human control subjects (NCS).

2. [Ca2+]i was significantly higher in the platelets of 8- and 20-week-old SHR in comparison with WKY. However, no difference was evident after weaning. Changes of cellular calcium in hypertensive rats apparently evolved simultaneously with the development of high arterial pressure.

3. [Ca2+]i was significantly higher in platelets of EHP than in NCS.

4. In lymphocytes of SHR, [Ca2+]i was not different from WKY at 4 and 8 weeks, but was increased at 14 weeks and at older ages. In EHP, intralymphocytic [Ca2+] was only modestly higher than in controls. On the whole, the results suggest that control of cytoplasmic calcium in these blood cells is similarly affected in human and animal models of primary hypertension.
The effect of Airway Anaesthesia on the Control of Breathing and the Sensation of Breathlessness in Man
Authors: Winning A. J. , Hamilton R. D. , Shea S. A. , Knott C. , Guz A.
Published: August 2015

1. The effect on ventilation of airway anaesthesia, produced by the inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter = 4.77 μm), was studied in 12 normal subjects.

2. The dose and distribution of the aerosol were determined from lung scans after the addition to bupivacaine of 99mTc. Bupivacaine labelled in this way was deposited primarily in the central airways. The effectiveness and duration of airway anaesthesia were assessed by the absence of the cough reflex to the inhalation of three breaths of a 5% citric acid aerosol. Airway anaesthesia always lasted more than 20 min.

3. Resting ventilation was measured, by respiratory inductance plethysmography, before and after inhalation of saline and bupivacaine aerosols. The ventilatory response to maximal incremental exercise and, separately, to CO2 inhalation was studied after the inhalation of saline and bupivacaine aerosols. Breathlessness was quantified by using a visual analogue scale (VAS) during a study and by questioning on its completion.

4. At rest, airway anaesthesia had no effect on mean tidal volume (VT), inspiratory time (Ti), expiratory time (Te) or end-tidal Pco2, although the variability of tidal volume was increased. On exercise, slower deeper breathing was produced and breathlessness was reduced. The ventilatory response to CO2 was increased.

5. The results suggest that stretch receptors in the airways modulate the pattern of breathing in normal man when ventilation is stimulated by exercise; their activation may also be involved in the genesis of the associated breathlessness.

6. A hypothesis in terms of a differential airway/alveolar receptor block, is proposed to explain the exaggerated ventilatory response to CO2.
Comparative Study of Serum Amyloid A Protein and C-Reactive Protein in Disease
Authors: Maury C. P. J.
Published: August 2015

1. On the basis of results from 3000 parallel measurements of serum amyloid A protein (SAA) and C-reactive protein (CRP) in various clinical and experimental conditions, the relationship between these proteins was examined and the question of whether measurements of SAA can provide clinically useful information beyond that from CRP assays was evaluated.

2. The concentrations of SAA and CRP showed a close relationship in a wide range of clinical conditions and the general clinical impact of an elevated SAA or CRP level is similar. SAA was, however, more sensitive than CRP in reflecting inflammatory activity, and in some conditions characterized by normal or only slightly elevated CRP concentrations, measurements of SAA concentrations could be used for monitoring disease activity and response to treatment.

3. Marked variation in the ratios of SAA to CRP concentration occurred in response to different stimuli (e.g. surgical trauma/immunological tissue injury), suggesting the existence of independent, disease-specific pathways of regulation for the serum concentrations of SAA and CRP.
Mechanism of increased plasma urea after diuretic therapy in uraemic patients
Authors: Canton Antonio Dal , Fuiano Giorgio , Conte Giuseppe , Terribile Maurizio , Sabbatini Massimo , Cianciaruso Bruno , Andreucci Vittorio E.
Published: August 2015

1. To clarify why diuretic therapy raises plasma urea in patients with chronic renal failure, three groups of uraemic subjects were treated with frusemide for 6 days.

2. In group 1 (n = 9), frusemide significantly decreased body weight and increased average plasma urea from 18.7 mmol/l to 28.8 mmol/l (P<0.001). this rise in plasma urea was secondary to reduced urea excretion, which occurred in spite of an increase in urea filtration.

3. In group 2 (n = 7), frusemide was associated with salt replacement, in order to prevent salt depletion; in these patients neither reduction in urea excretion nor increase in plasma urea occurred.

4. In group 3 (n = 10), the marked diuretic-induced fall in urea clearance was found to be independent of enhanced proximal tubular re-absorption (measured in water diuresis).

5. These results show that the rise in plasma urea is due to increased tubular reabsorption of urea, presumably in the distal part of the nephron, secondary to extracellular fluid (ECF) volume depletion.
Altered metabolism of low density lipoprotein in humans after prolonged incubation in plasma
Authors: Kostner G. M. , Krempler F. , Dieplinger H. , Zechner R. , Teubl I. , Sandhofer F.
Published: August 2015

1. Lecithin: cholesterol acyltransferase (LCAT) in combination with exchange and transfer proteins is known to alter the composition of all plasma lipoprotein fractions.

2. Human plasma from healthy donors was incubated for 24 h at 37°C in the absence and at 4°C and at 37°C in the presence of the LCAT inhibitors sodium iodoacetate (5 mmol/l), and the low density lipoprotein fractions (LDL) were isolated.

3. LDL isolated from LCAT-active plasma (LDL-a) exhibited pronounced alterations in their surface material: the relative content of phospholipids and of free cholesterol was reduced and the content of tetramethylurea-soluble apolipoproteins was increased. LDL isolated from plasma incubated at 37°C with or without sodium iodoacetate showed significantly increased triglyceride concentrations.

4. The LDL fractions from LCAT-active and LCAT-inactive (LDL-i) incubates were iodinated with 125I and 131I respectively, and their metabolic behaviour was studied in humans.

5. LDL-a was cleared from circulation at a slower rate as compared with LDL-i (t1/2 = 3.17 ± 0.47 vs 2.88 ± 0.45 days). The apparent fractional catabolic rate of LDL-a, calculated according to a two-pool model, was reduced by 22.2 ± 3.1%. Comparing LDL-a with LDL isolated from LCAT-inactive plasma which had been incubated at 37°C, the changes in the metabolic variables were less pronounced.

6. It is concluded that physiological alterations of the chemical compositions, caused by LCAT and exchange/transfer proteins, influence the metabolism of LDL.
Is salt reabsorption in the human sweat duct subject to control?
Authors: Schwarz V. , Simpson I. M. Naomi
Published: August 2015

1. There is a time lag between the beginning of sweat secretion and fully effective production of fluid of minimum salt content. It is suggested that changes in permeability to water or electrolytes have to be effected and may account for the time lag.

2. The composition of thermal and pilocarpine sweat indicates that pharmacological stimulation does not wholely reproduce the physiological mechanism: pilocarpine sweat contains more sodium and more cyclic AMP, irrespective of the secretory rate.

3. The sweat obtained from patients with cystic fibrosis has been compared with that from normal children: the concentrations of cyclic AMP and cyclic GMP are the same. Defective sodium reabsorption in the patients is therefore unlikely to be due to inadequate or excessive synthesis of these cyclic nucleotides.
Haemodynamics of renal artery stenosis (a comment based on Ohm's law)
Authors: Huisman R. M. , de Zeeuw D.
Published: August 2015

The transient and steady-state effects of renal artery stenosis are of great physiological and clinical interest. Important research on this subject has been done by Korner and Anderson from Melbourne, Australia. Much of their work has recently been summarized by Korner in the 1982 supplement issue of Clinical Science [1]. Although their conclusions are in general undoubtedly correct, we have some objections to details of their theoretical concepts which we would like to discuss here. The great impact of their work makes it desirable in our view to give wider exposure to our objections. As it happens, both points which we would like to make can be related to Ohm's law(V = I × R).
Blood pressure recording in the ambulatory patient and evaluation of cardiovascular risk
Authors: Brunner Hans R. , Waeber Bernard , Nussberger Jürg
Published: August 2015

Many large epidemiological studies, such as the one going on in Framingham [1], have clearly established that hypertension is one of the major risk factors for cardiovascular diseases. Well controlled intervention trials have also clearly demonstrated that antihypertensive therapy can significantly reduce the incidence of complications such as stroke, congestive heart failure and possibly myocardial infarction [2-4]. There exists no doubt about the important causal relationship between elevated blood pressure and cardiovascular complications. The measurement of blood pressure has thus become one of the most frequent procedures carried out by any practising physician. Notwithstanding, some doubt has been expressed whether all patients with a slightly elevated blood pressure at the physician's office are indeed prone to suffer a heart attack or a stroke and need lifelong antihypertensive therapy [5, 6]. Does the casual blood pressure measurement at the physician's office accurately assess the risk of each individual patient of suffering a heart attack in the future?
Urinary kallikrein and systemic prostacyclin synthesis during sodium chloride infusion in normal man
Authors: Watson M. L. , Cumming A. D. , Lambie A. T. , Oates J. A.
Published: August 2015

1. An intravenous infusion of 3 litres of sodium chloride solution (saline: 150 mmol/l) was given over 1 h to normal subjects.

2. During and immediately after the infusion, renal plasma flow increased in the majority of subjects, but the rise was not statistically significant. Significant increases in urine flow, sodium excretion, urinary kallikrein excretion and urinary excretion of dinor-6-keto prostaglandin (PG) F1α, a measure of systemic PGI2 synthesis, were noted. Plasma renin activity and plasma protein concentration were significantly lowered by the infusion.

3. At 2 h after the end of the infusion, although urine flow fell significantly, sodium excretion had not decreased. The reduction in plasma renin activity and plasma proteins persisted, and excretion of kallikrein and the PGI2 metabolite returned to control values.

4. Overall, urinary kallikrein excretion correlated significantly with urine flow and with sodium excretion. Peak kallikrein excretion occurred in the second 30 min of the infusion, and preceded maximal urine flow and sodium excretion.

5. The results suggest that increased systemic synthesis of PGI2 occurs in response to an acute infusion of sodium chloride, and may be an adaptive response of the vasculature to volume expansion. They support a role for the renal kallikrein-kinin system in the early diuretic and natriuretic response to saline infusion; the reduction in plasma renin activity and plasma protein concentration may be involved in both the early response and the persistent natriuresis 2 h after the infusion.
Renin-aldosterone system suppression during water immersion in renovascular hypertension
Authors: Coruzzi P. , Biggi A. , Musiari L. , Ravanetti C. , Novarini A.
Published: August 2015

1. We studied renin-aldosterone system behaviour in five renovascular hypertensive patients during central hypervolaemia by water immersion to the neck.

2. Water immersion significantly suppressed the high peripheral renin levels of the patients despite an autonomic renin secretion from the stenotic kidney, a significant reduction of mean blood pressure and an increase in distal tubule sodium concentration.

3. The effect of immersion on plasma aldosterone appeared to be primarily mediated via suppression of plasma renin activity (PRA).

4. Our data suggest that: (a) the renin secretion is mainly modulated by cardiopulmonary receptors activity; (b) the neurogenic reflex control of plasma renin activity is very effective in renovascular hypertension.
Reflex vascular responses in the finger to contralateral thermal stimuli during the normal menstrual cycle: a hormonal basis to Raynaud's phenomenon?
Authors: Lafferty K. , Trafford J. C. De , Potter C. , Roberts V. C. , Cotton L. T.
Published: August 2015

1. Raynaud's phenomenon is a condition which primarily affects women and it must be assumed that hormonal influences are responsible.

2. To further investigate this assumption the effect of cyclic sex hormone fluctuations on the digital vascular reactivity of ten normal young women was studied by the diagnostic techniques of thermal entrainment of finger blood flow and Doppler ultrasound mapping of the digital arteries.

3. In the immediate pre-ovulatory period the results obtained were comparable with those found in patients with established Raynaud's phenomenon, suggesting that oestrogen has an important modulating effect in vivo on reflex peripheral vasomotor responses to thermal stimuli.

4. ‘Primary’ Raynaud's phenomenon may represent an exaggerated response to oestrogen.
Modulation of postjunctional α-adrenergic responsiveness by local changes in temperature
Authors: Vanhoutte P. M. , Cooke J. P. , Lindblad L.-E. , Shepherd J. T. , Flavahan N. A.
Published: August 2015

1. In canine cutaneous veins, local moderate warming (37°-41°C) augments the responsiveness to postjunctional α1-adrenergic stimulation but depresses that to postjunctional α2-adrenergic activation. Moderate cooling (37°-24°C) has the opposite effect.

2. The effects of warming and cooling on α1-adrenergic responses are buffered by a large receptor reserve, allowing for the predominance of alterations in α2-adrenergic responsiveness.
Effects of desipramine on stimulation-induced contractions of the vas deferens of rats pretreated either chronically with desipramine or acutely with idazoxan
Authors: Doxey J. C. , Roach A. G. , Samuel J.
Published: August 2015

1. In the present studies the effects of desipramine on the functional sensitivity of the prejunctional α2-adrenoceptors of the vas deferens were studied in pithed rats; contractions of the tissue were evoked by electrical stimulation (6 Hz) of the spinal sympathetic outflow.

2. Twenty-four hours after a single dose of desipramine (10 mg/kg, intraperitoneally) the inhibitory dose-response curves to either UK 14 304 or desipramine itself did not differ significantly from those seen in control animals, whereas both were displaced significantly to the right after 15 days pretreatment with desipramine. Thus the functional responsiveness of the prejunctional α2-adrenoceptors of the vas deferens was reduced by chronic but not acute pretreatment with desipramine.

3. In acute studies desipramine (0.3-4.3 mg/kg, intravenously) inhibited electrically induced contractions of the vas deferens of pithed rats. In the presence of the selective α2-adrenoceptor antagonist idazoxan (1 mg/kg, intravenously) desipramine potentiated nerve stimulation.

4. Although idazoxan (10-1440 μg/kg, intravenously) itself potentiated electrically induced contractions of the vas deferens the potentiation observed was markedly less than that obtained in rats pretreated acutely with desipramine (0.3 mg/kg, intravenously).

5. Acute simultaneous blockade of both prejunctional α2-adrenoceptors and uptake into nerve terminals can produce maximal potentiation of the contraction of the vas deferens to sympathetic nerve stimulation.

6. Results are discussed in relation to the hypothesis that the combination of an uptake inhibitor and a prejunctional α2-adrenoceptor antagonist, by enhancing noradrenergic transmission, may provide an antidepressant therapy with rapid onset of action.
Effects of Small-Particle Aerosols of Local Anaesthetic on Dyspnoea in Patients with Respiratory Disease
Authors: Stark R. D. , O'neill P. A. , Russell N. J. W. , Heapy C. G. , Stretton T. B.
Published: August 2015

1. This study was devised to test the hypothesis that dyspnoea could be mediated by unmyelinated vagal sensory nerve endings (type J receptors) situated at alveolar level in the lung.

2. A modified jet nebulizer was used to generate an aerosol of local anaesthetic in particles small enough to allow alveolar deposition. Lignocaine (2% and 5%) produced aerosols with an arithmetic mean diameter (+sd) of 1.5+0.3 and 1.2+0.6 μm respectively, the mass median diameters being 1.7 (geometric standard deviation = 1.2) and 2.5 (geometric standard deviation = 1.7) μm respectively.

3. In experimental animal models a vagally mediated tachypnoea may be induced acutely by pulmonary microembolism. This response is known to be mediated by unmyelinated pulmonary afferent nerves in the vagus. Local anaesthetic agents administered as small particles, but not as large particles, obtunded this response, which suggests that the aerosol was capable of penetration to alveolar level.

4. Upon this background, a clinical study was designed to compare the effects of lignocaine with placebo both given as small-particle aerosols. Six patients, including two with diffuse alveolar pathology and four with chronic airflow obstruction, were studied. Respiratory frequency was determined before and after the aerosol, and exercise tolerance and breathlessness were measured with a 6 min walking test and visual analogue scales.

5. After lignocaine there was no clinical evidence of anaesthesia of the upper airways but bronchoconstriction occurred. While no overall effect of lignocaine on dyspnoea was apparent, individual patients showed some evidence of benefit. Although other factors deserve consideration, the lack of a dramatic effect on dyspnoea suggests that dyspnoea in such patients is not mediated principally by J receptors.
Circulating Histamine and Neutrophil Chemotactic Activity During Allergen-Induced Asthma: The Effect of Inhaled Antihistamines and Anti-Allergic Compounds
Authors: Morgan D. J. R. , Moodley I. , Cundell D. R. , Sheinman B. D. , Smart W. , Davies R. J.
Published: August 2015

1. Plasma histamine and serum neutrophil chemotactic activity (S-NCA) were measured in ten atopic asthmatic patients on four separate occasions after allergen bronchial provocation testing (BPT).

2. Single doses of inhaled sodium cromoglycate (SCG; 20 mg), clemastine (0.5 mg), ketotifen (0.5 mg) and isotonic saline (0.9% NaCl) placebo were administered 30 min before bronchial provocation testing in random order and double-blind.

3. The airflow obstruction after BPT was monitored by measurement of forced expiratory volume in 1s (FEV1). Plasma histamine was measured by the double-isotope radioenzymatic assay and S-NCA by a modified Boyden chamber technique.

4. A highly significant decrease in FEV1 after BPT occurred on the placebo pre-treatment visit (P < 0.001). Prior administration of inhaled SCG, clemastine and ketotifen significantly reduced the decrease in airflow obstruction seen after BPT when compared with placebo treatment (P < 0.01, P < 0.02, P < 0.05 respectively).

5. No significant alteration in plasma histamine was detected during allergen-induced airflow obstruction.

6. Levels of S-NCA were significantly higher 5, 10 and 15 min after BPT when compared with the pre-challenge level (P < 0.01, P < 0.01, P < 0.001 respectively). These levels were not significantly decreased when airflow obstruction was inhibited by the prior inhalation of SCG, clemastine or ketotifen.
The Maximal Sniff in the Assessment of Diaphragm Function in Man
Authors: Miller Juliet M. , Moxham John , Green Malcolm
Published: August 2015

1. We studied diaphragm function in a total of 64 normal subjects, who had no past or present respiratory or neuromuscular impairment.

2. We measured transdiaphragmatic pressure (Pdi) during maximal sniffs and compared these values with Pdi during maximal static inspiratory efforts (PImax.).

3. The range of Pdi during maximal sniffs (82-204 cm H2O) had better defined lower limits than Pdi during PImax. (16-164 cm H2O) and a higher mean value : mean + sd for maximal sniffs was 137 + 28 cm H2O and for PImax. was 90 + 37 cm H2O.

4. The reproducibility of sniff Pdi was assessed in eight randomly chosen subjects over 3 days: the mean coefficient of variation was 7.2%. By comparison the coefficient of variation of Pdi during PImax. was 13.0% in seven subjects.

5. The maximal sniff is a spontaneous manoeuvre, easily performed, repeatable without tiring, and reproducible. Its measurement provides a more reliable quantitative method for assessment of diaphragm strength, which has potential in clinical practice.
Role of the Renal Nerves in Modulating Renin Release During Pressure Reduction at the Feline Kidney
Authors: Johns Edward J.
Published: August 2015

1. Experiments were undertaken in pentobarbitone-anaesthetized cats to determine how reflex activation of the renal nerves altered the responsiveness of the kidney to release renin during reductions in renal perfusion pressure. Reflex activation of the renal nerves was achieved by reducing carotid sinus perfusion pressure by 30 mmHg, which increased systemic blood pressure. During this period renal perfusion pressure was regulated at control levels and neither renal blood flow nor glomerular filtration rate changed, but there was a significant decrease in sodium excretion and increase in renin secretion. Renal denervation abolished both these latter responses.

2. Renal perfusion pressure reduction, by 25-30 mmHg, had no effect on renal blood flow or glomerular filtration rate but significantly decreased sodium excretion and increased renin secretion. Simultaneous reduction of carotid sinus and renal perfusion pressures had no effect on renal blood flow or glomerular filtration rate, decreased sodium excretion, and the magnitude of the increase in renin secretion was significantly greater than that obtained with reduction in renal perfusion pressure alone. Renal denervation abolished the increase in renin secretion during these manoeuvres.

3. During atenolol administration, renal haemodynamics and sodium excretion responses to renal pressure reduction were similar to those obtained in the absence of the drug. Renin secretion was increased, but significantly less than in the absence of atenolol. Simultaneous carotid sinus and renal pressure reductions during atenolol administration had no effect on renal haemodynamics, reduced sodium excretion and increased renin secretion, the magnitude of which was significantly greater than that recorded with only renal pressure reduction in the presence of atenolol.

4. Direct electrical stimulation of the renal nerves, at frequencies which caused a 5-10% reduction in renal blood flow, did not change glomerular filtration rate, decreased sodium excretion by 30% and increased the rate of renin secretion twofold. In the presence of atenolol, such renal nerve stimulation reduced renal blood flow to the same degree, did not change filtration rate, decreased sodium excretion by 37% but did not change renin secretion.

5. These results show that the magnitude of the release of renin in response to renal pressure reduction is dependent on activity within the renal nerves, being blunted after denervation, and enhanced during reflex activation of the renal nerves.