bluuebunny/crossref_metadata_2025 huggingface dataset:
Na+/H+ antiport and buffering capacity in human polymorphonuclear and mononuclear leucocytes
Authors: Frighi V. , Ng L. L. , Lewis A. , Dhar H.
Published: August 2015

1. Na+/H+ antiport activity was measured in peripheral blood polymorphonuclear and mononuclear cells of 12 healthy subjects by using an intracellular pH clamp technique to determine the external Na+-dependent H+ efflux rate in cells loaded with a pH-sensitive fluorescent dye, bis(carboxyethyl)carboxyfluorescein. The change in external Na+ concentrations for all pH measurements was similar in both cell types.

2. A significant difference between the two types of cells was found, the polymorphonuclear leucocytes having a higher Na+/H+ antiport activity than the lymphocytes. Cellular intrinsic buffering capacity measured in the absence of HCO−3 was also higher in the polymorphonuclear cells than in the lymphocytes.

3. These differences may be associated with a difference in the role of the Na+/H+ exchanger in these two types of cells, although in vivo the presence of HCO−3/Cl− exchangers may also contribute to intracellular pH homoeostasis.
The contribution of the large intestine to blood acetate in man
Authors: Scheppach W. , Pomare E. W. , Elia M. , Cummings J. H.
Published: August 2015

1. To test the hypothesis that the colon contributes significantly to venous plasma acetate concentrations, experiments were carried out in healthy volunteers and ileostomy patients.

2. Fasting plasma acetate levels were measured in 10 ileostomy patients and compared with those in 21 control subjects. Values in ileostomy patients (21.3 ± 0.8 μmol/l) were significantly lower than in control subjects (48.0 ± 4.2 μmol/l).

3. Plasma acetate concentration was estimated in eight healthy volunteers during 108 h of continuous fasting. Acetate concentrations rose significantly from 12 h (43.9 ± 4.4 μmol/l) to 108 h of starvation (114.0 ± 15.6 μmol/l) and fell back to normal fasting values on refeeding and another 12 h fast (44.3 ± 4.7 μmol/l).

4. When colonic fermentation was stimulated after oral ingestion of 10 g of lactulose, the plasma acetate concentration increased significantly (from 44.0 ± 7.4 to 114.4 ± 16.2 μmol/l) in seven healthy control subjects. This rise was not affected by concomitant dosage of metronidazole.

5. These data suggest that there are at least two major sources of acetate in man, an endogenous source and the colon which probably becomes more important when fermentation of carbohydrate is occurring.
Transcription, storage and release of atrial natriuretic factor in the failing human heart
Authors: Fischer Thomas A. , Haass Markus , Dietz Rainer , Willenbrock Roland C. , Saggau Werner , Lang Rudolf E. , Kübler Wolfgang
Published: August 2015

1. In this study the relationship between the synthesis of atrial natriuretic factor at the level of atrial natriuretic factor mRNA and the atrial storage and circulating plasma levels of atrial natriuretic factor were investigated in 15 patients with heart failure. The patients underwent right and left heart catheterization before cardiac surgery for valve replacement or coronary artery bypass grafting.

2. Plasma concentrations of atrial natriuretic factor were correlated to atrial levels of atrial natriuretic factor mRNA. Atrial levels of atrial natriuretic factor mRNA and plasma concentrations of atrial natriuretic factor exhibited a close correlation to both pulmonary artery pressure and left atrial pressure. No relationship, however, could be found between the right atrial content of atrial natriuretic factor and both the expression of atrial natriuretic factor mRNA in the atria and the plasma levels of atrial natriuretic factor.

3. From these data it may be concluded that increased plasma levels of atrial natriuretic factor in the pressure-and/or volume-overloaded heart are associated with an elevated level of atrial natriuretic factor mRNA. We suggest that not only plasma levels of atrial natriuretic factor but also the expression of atrial natriuretic factor in the atria are related to left ventricular filling pressures in the failing human heart.
Role of the wrist cuff in forearm plethysmography
Authors: Lenders Jacques , Janssen Geert-Jan , Smits Paul , Thien Theo
Published: August 2015

1. To determine whether a wrist cuff is necessary to measure the forearm blood flow correctly, we studied the effects of wrist cuff inflation to supra-venous and supra-systolic pressure values over a large range of forearm blood flow values: in the basal state, during post-occlusive hyperaemia of the hand, and during heating of the hand with warm air. Eleven healthy men participated, and the study was carried out at two different ambient temperatures of 20 and 25°C.

2. In the basal state, the measured forearm blood flow was lowest with the wrist cuff at supra-systolic pressure. With the wrist cuff at supra-venous pressure the forearm blood flow was also lower than with an uninflated cuff, but only significantly so when the basal forearm blood flow was higher (at a room temperature of 25°C).

3. During post-occlusive hyperaemia, inflating the wrist cuff to supra-systolic pressure produced the lowest forearm blood flow value at both room temperatures. In addition, with the wrist cuff at supra-venous pressure, forearm blood flow values were lower than with the uninflated cuff, but the supra-venous cuff pressure was clearly less efficient in excluding the hand blood flow than the supra-systolic cuff pressure.

4. During heating of the hand, both supra-systolic and supra-venous cuff pressures were effective in excluding the hand blood flow at both room temperatures. The forearm blood flow measured with the wrist cuff at supra-systolic pressure was lower than that measured with the wrist cuff at supra-venous pressure, but the difference was only significant at a room temperature of 20°C.

5. In conclusion, we have demonstrated that a wrist cuff at supra-systolic pressure is most appropriate for the exclusion of the hand circulation in order to measure the forearm blood flow correctly.
Renal sensitivity to endothelium-derived-relaxing-factor-mediated vasodilatation in the spontaneously hypertensive rat
Authors: Burton G. A. , Haylor J. , de Jonge A.
Published: August 2015

1. The sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation has been investigated in the spontaneously hypertensive rat and the Wistar-Kyoto normotensive rat using an isolated perfused rat kidney model.

2. No difference in the slope, ED50 or maximum of the concentration-response curves for the endothelial-dependent vasodilators A23187, a calcium ionophore, and acetylcholine could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats.

3. No difference in the slope or the ED50 of the concentration-response curve for the endothelial-independent vasodilators, atrial natriuretic factor and sodium nitroprusside, could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats. However, in the spontaneously hypertensive rats, the maximum vasodilator response to atrial natriuretic factor, but not to sodium nitroprusside, was increased.

4. The perfused kidney from the spontaneously hypertensive rat also showed an increase in the maximum but not in the slope or ED50 of the concentration-response curve for vasoconstriction induced by the α1-adrenoceptor agonist methoxamine.

5. The involvement of endothelium-derived relaxing factor in mediating the renal vasodilator response to A23187 and acetylcholine was confirmed in experiments performed in perfused kidneys obtained from normotensive Wistar rats.

6. It is concluded that the sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation is not modified in the spontaneously hypertensive rat. This does not, however, exclude a role for the synthesis of endothelium-derived relaxing factor in the maintenance of blood pressure in the spontaneously hypertensive rat.
Effects of treatment with nasal continuous positive airway pressure on atrial natriuretic peptide and arginine vasopressin release during sleep in patients with obstructive sleep apnoea
Authors: Krieger J. , Follenius M. , Sforza E. , Brandenberger G. , Peter J. D.
Published: August 2015

1. Patients with obstructive sleep apnoea have increased diuresis during sleep, which decreases with nasal continuous positive airway pressure treatment. These changes have been attributed to an increased release of atrial natriuretic peptide in obstructive sleep apnoea, and its decrease with continuous positive airway pressure treatment.

2. In order to clarify the change in plasma atrial natriuretic peptide level and to investigate the underlying mechanisms, blood samples were taken at 10 min intervals from nine patients with obstructive sleep apnoea during two nights when the patients were either untreated or treated with continuous positive airway pressure. Polysomnographic monitoring, including transcutaneous oximetry, and measurement of oesophageal pressure were performed simultaneously. Plasma arginine vasopressin was also measured.

3. The plasma level of arginine vasopressin did not change. The level of atrial natriuretic peptide was high and exhibited secretion bursts in six out of the nine patients; it drastically decreased with continuous positive airway pressure treatment.

4. Across the patients, the mean plasma levels of atrial natriuretic peptide was correlated with the degree of hypoxaemia and the degree of oesophageal pressure swings during the sleep apnoeas.

5. Within the patients, cross-correlation studies suggested that the atrial natriuretic peptide secretory bursts were related either to the oesophageal pressure swings or to the apnoea-related hypoxaemia.

6. We conclude that release of atrial natriuretic peptide decreases with continuous positive airway pressure treatment in those patients with obstructive sleep apnoea who have increased release of atrial natriuretic peptide before treatment.

7. The results are in agreement with the hypothesis that the haemodynamic changes induced by the increased swings in intra-thoracic pressure during ineffective respiratory efforts or by the hypoxia-induced vasoconstriction play a role in these changes.
Plasma profiles and removal rates of inorganic sulphate, and their influence on serum ionized calcium, in patients on maintenance haemodialysis
Authors: Marangella M. , Petrarulo M. , Cosseddu D. , Vitale C. , Linari F.
Published: August 2015

1. Regular dialysis treatment is reported to remove inorganic sulphate, but not to restore its level to normal. To evaluate the adequacy of modern dialysis techniques in maintaining the sulphate balance, intra- and inter-dialysis plasma profiles and removal rates of sulphate were studied in 20 stable patients on maintenance haemodialysis. The influence of sulphate levels on the distribution of calcium-complex species was also investigated.

2. Sulphate was determined by ion-exchange chromatography of both serum ultrafiltrates, taken at the start of, during, at the end of, and at 24 h and 48 h after a dialysis session, and whole diffusate collections. Dialyser clearances of sulphate were assessed by two independent procedures and compared with those of urea and creatinine, on two different methods of dialysis, i.e. traditional haemodialysis with Cuprophan hollow fibre filters, and haemodiafiltration with high-flux Polysulphone or polyacrylonitrile dialysers. Concentrations of the main serum ions were determined before and after dialysis and used to solve a multiple mass balance equation system by which concentrations of the calcium-complex species were calculated.

3. Before dialysis, sulphate levels were eight times those determined in 17 control subjects and remained higher than normal at the end of dialysis. These changes were independent of the dialysis procedure. There was a close correlation between serum levels of sulphate and creatinine. Dialyser clearances of sulphate were comparable with those of creatinine, but lower than those of urea. Clearances of all solutes were higher on haemodiafiltration.

4. The mean removal of sulphate during a single session was about 30 mmol; the estimated removal rate averaged 15 mmol/day and was closely related to the protein catabolic rate as derived by urea kinetic modelling. Removal rates were slightly lower than rates of sulphate excretion in 40 control subjects. Because serum sulphate levels were quite stable over time this decrease was accounted for by a reduction in the net generation of sulphate, due to either altered catabolism of sulphur-containing amino acids or reduced intakes of animal protein.

5. The distribution of calcium-complex species demonstrated that the calcium-sulphate complex concentration in pre-dialysis samples was similar to that of calcium-phosphate complex and both were markedly increased as compared with normal subjects. Dialysis minimized but did not cancel out these abnormalities, which were responsible for significant decreases in free calcium concentration.

6. It is concluded that, although dialysis efficiently removes newly generated inorganic sulphate, it does not prevent chronic increases in this anion. Inadequate control of plasma sulphate levels by dialysis or through the diet may adversely affect the clinical state of uraemic patients and induce pervasive changes in calcium homoeostasis.
Noradrenaline release in skeletal muscle and in adipose tissue studied by microdialysis
Authors: Grønlund Bo , Astrup Arne , Bie Peter , Christensen Niels Juel
Published: August 2015

1. In adipose tissue and in skeletal muscle the extracellular noradrenaline levels were studied by microdialysis in the conscious dog and compared with the noradrenaline concentration in arterial plasma.

2. The experiments were performed with and without tyramine added to the perfusion medium, and noradrenaline was measured by a sensitive radioenzymic assay.

3. In the absence of tyramine, the interstitial noradrenaline levels in adipose tissue and skeletal muscles were similar to arterial blood concentrations, provided that the former were corrected for recovery. The recovery estimated from experiments in vitro averaged 16% at room temperature.

4. With tyramine added to the perfusates, noradrenaline levels increased 10-fold. Arterial noradrenaline concentrations did not change, indicating that noradrenaline was released only locally in the tissue.

5. Our results indicate that the microdialysis technique combined with a sensitive assay for measuring noradrenaline may be applicable to the assessment of local noradrenaline release in adipose tissue and in skeletal muscle. This may be of interest, especially in adipose tissue during physiological stimulation in which sympathetic activity is difficult to evaluate by other techniques.
Cigarette smoking and urinary excretion of markers for platelet/vessel wall interaction in healthy women
Authors: Rångemark C. , Wennmalm Å.
Published: August 2015

1. Cigarette smoking is known to increase the risk of cardiovascular disease in both men and women. Experimental and epidemiological studies have demonstrated that cigarette smoking is associated with several indices of increased platelet activation and platelet/vessel wall interaction in men. The aim of the present study was to test the hypothesis that cigarette smoking is linked to an increased platelet activity in women also.

2. In 26 healthy smoking and non-smoking women (age 21–49 years) the urinary excretion of the thromboxane A2 metabolite 2,3-dinor-thromboxane B2 (an index of platelet activation) and of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1α (an index of platelet/vessel wall interaction) were analysed by g.c.-m.s. in samples collected on days 3, 10 and 20 of their respective menstrual cycles.

3. The urinary excretion of 2,3-dinor-thromboxane B2 did not vary significantly during the menstrual cycle, either in the smokers or in the non-smokers. It was consistently higher (P < 0.004) in the group of smokers (average of days 3, 10 and 20, 395 ± 61 pg/mg of creatinine; mean ± sem) than in the group of non-smokers (average 188 ± 22 pg/mg of creatinine).

4. The urinary excretion of 2,3-dinor-6-keto-prostaglandin F1α did not differ between the groups on any of the days studied (average on days 3, 10 and 20 in the smokers and non-smokers was 281 ± 50 and 227 ± 30 pg/mg of creatinine, respectively).

5. These data demonstrate that smoking fertile women excrete more of the thromboxane A2 metabolite than do non-smokers, thereby supporting the hypothesis that cigarette smoking elicits platelet activation in healthy women. In contrast, platelet/vessel wall interaction does not appear to be facilitated in smoking compared with non-smoking women. The data suggest that platelet activation is not a major haemostatic mechanism during menstruation.
Increased plasma cholecystokinin levels and small gall bladders in adult patients with cystic fibrosis
Authors: van Haren E. H. J. , Hopman W. P. M. , Jansen J. B. M. J. , Rosenbusch G. , Lamers C. B. H. W. , van Herwaarden C. L. A.
Published: August 2015

1. In patients with cystic fibrosis, abnormalities in plasma cholecystokinin level and gall-bladder emptying may contribute to the development of maldigestion and gall-stones.

2. Therefore, we have measured plasma cholecystokinin levels and gall-bladder volumes before and after ingestion of a standard breakfast in eight adult patients with cystic fibrosis and in eight normal control subjects.

3. In the patients with cystic fibrosis basal (2.8 ± 0.4 pmol/l; P < 0.05, t-test) and maximum post-prandial (5.7 ± 0.5 pmol/l; P < 0.05, t-test) plasma cholecystokinin levels were significantly higher than those in the control subjects (1.9 ± 0.1 pmol/l, and 4.5 ± 0.2 pmol/l, respectively). On the other hand, integrated plasma cholecystokinin secretion in response to the meal was similar (t-test, P = 0.4 versus control subjects). The increased plasma cholecystokinin levels in the patients with cystic fibrosis were accompanied by reduced gallbladder volumes in both the basal (7.8 ± 2.1 cm3 versus 20.9 ± 2.3 cm3 in control subjects; P < 0.005, t-test) and the post-prandial state (2.2 ± 1.0 cm3 versus 4.8 ± 0.8 cm3 in control subjects; P = 0.06, t-test). Gall-bladder emptying in the patients with cystic fibrosis was well preserved (70 ± 7% versus 78 ± 9% in control subjects; P = 0.4, t-test).

4. In comparison with normal control subjects, patients with cystic fibrosis have an increased basal plasma cholecystokinin level and a reduced gall-bladder volume, whereas post-prandial gall-bladder emptying and plasma cholecystokinin secretion are not significantly different. In cystic fibrosis, neither impaired cholecystokinin release nor impaired gall-bladder emptying appear to play a role in the pathogenesis of either gall-stones or maldigestion.
A defect in insulin release in women at risk of future non-insulin-dependent diabetes
Authors: Dornhorst Anne , Edwards Simon G. M. , Nicholls Jonathan S. D. , Anyaoku Victor , Mclaren Duncan , Heslop Kirsten E. , Elkeles Robert S. , Beard Richard W. , Johnston Desmond G.
Published: August 2015

1. A study on seven Caucasian glucose-tolerant women with previous gestational diabetes and seven matched control subjects is presented. The insulin response to oral glucose, insulin sensitivity and fasting glucose production rates were measured by using a 75 g oral glucose tolerance test, an insulin tolerance test and a non-radioactive tracer, [6,6-2H]glucose, respectively.

2. Fasting plasma glucose levels were similar between the women with previous gestational diabetes and the control subjects (4.8 ± 0.3 versus 4.7 ± 0.2 mmol/l), as were fasting plasma insulin levels (median 4 m-units/l, range 1–13 m-units/l versus median 4 m-units/l, range 1–24 m-units/l). After oral glucose the 60 min plasma glucose levels in the women with previous gestational diabetes were significantly higher (8.5 ± 0.6 versus 6.7 ± 0.8 mmol/l, P < 0.05), whereas the plasma insulin level was significantly lower at both 30 min (median 23 m-units/l, range 4–47 m-units/l versus median 55 m-units/l, range 23–100 m-units/l, P < 0.02) and at 60 min (median 23 m-units/l, range 4–43 m-units/l versus median 60 m-units/l, range 16–126 m-units/l, P< 0.02).

3. Insulin sensitivity, expressed as the slope of the regression line of plasma glucose level against time after intravenous infusion of insulin (0.05 unit/kg), was similar in the women with previous gestational diabetes and the control subjects (mean slope, −0.17 ± 0.01 versus −0.17 ± 0.01).

4. Fasting glucose production rates were similar in the women with previous gestational diabetes and the control subjects (2.2 ± 0.3 versus 1.9 ± 0.1 mg min−1 kg−1).

5. Women with previous gestational diabetes, a group at risk of future non-insulin-dependent diabetes, have abnormalities of insulin release at a time when insulin sensitivity and fasting glucose production are normal.
Metalloproteinases in degenerative aortic disease
Authors: Vine N. , Powell Janet T.
Published: August 2015

1. Atherosclerosis and aneurysm of the abdominal aorta are associated with thinning of the medial connective tissue. We have investigated the presence of the connective-tissue-degrading metalloproteinases in homogenates prepared from atherosclerotic, aneurysmal and control aortic media.

2. Gelatinase activity was much increased in homogenates from atherosclerotic and aneurysmal aorta [10.911.8 and 13.3 ± 3.3 μg of gelatin hydrolysed h−1 (mg of protein)−1 respectively]. This gelatinase activity was highest at the luminal aspect of the aortic media, where the activity increased three-to five-fold after the destruction of α2-macroglobulin. Zymograms demonstrated the principal gelatinase in atherosclerotic aorta to have a molecular mass of about 92 kDa, whereas in aneurysmal aorta there was a spectrum of gelatinase activity from 92 to 55 kDa.

3. Collagenase and stromelysin (proteoglycanase) could be detected by immunoblotting in homogenates of aneurysmal aorta, but rarely in atherosclerotic aorta and never in control aorta. Collagenase and stromelysin activities were low, but increased two-to three-fold after the destruction of tissue inhibitor of metalloproteinases. Collagenase and stromelysin activities were highest at the adventitial aspect of aneurysmal media.

4. The secretion of gelatinase by inflammatory cells at the intima of diseased aorta could have a pathological role in establishing atherosclerotic plaques and medial thinning. Secretion of collagenase, gelatinase and stromelysin from the adventitia could accelerate connective tissue degradation in the media of aneurysmal aorta.
Spectrum of orthostatic disorders: Classification based on an analysis of the short-term circulatory response upon standing
Authors: Wieling W. , ten Harkel A. D. J. , van Lieshout J. J.
Published: August 2015

1. In 31 consecutively referred patients (20 females, 11 males) with overt or suspected orthostatic disorders, the changes in blood pressure and heart rate that occur in the first 2 min of standing were analysed.

2. Blood pressure was measured continuously by Finapres. The blood pressure and heart rate responses after 1–2 min of standing (early steady-state response) were used to classify the patients as follows: group I (n = 17, age 42 ± 17 years), normal early steady-state blood pressure and heart rate responses; group II (n = 5, age 40 ± 14 years), combination of normal early steady-state blood pressure and postural tachycardia; group III (n = 9, age 51 ± 14 years), hypotensive orthostatic response with (4/9) or without (5/9) postural tachycardia. We examined whether additional information could be obtained by beat-to-beat analysis of the initial circulatory response (first 30 s). It was quantified by identifying the blood pressure trough and overshoot and the maximum heart rate and relative bradycardia.

3. The initial drop in systolic and diastolic blood pressures did not differ between the three groups. A recovery of blood pressure with a systolic and/or diastolic blood pressure overshoot was present in all group I and II patients, but was absent in all except two patients in group III. The initial maximum heart rate increase did not differ between the three groups. The relative bradycardia was less in groups II and III than in group I.

4. We conclude that analysis of the beat-to-beat blood pressure changes in the first 30 s after the onset of standing provides almost all the information that is necessary to determine abnormalities in orthostatic circulatory control.
Influence of nifedipine on cyclosporin A nephrotoxicity after unilateral nephrectomy in the spontaneously hypertensive rat
Authors: McNally P. G. , Baker F. , Mistry N. , Walls J. , Feehally J.
Published: August 2015

1. Nifedipine ameliorates cyclosporin A-induced renal impairment in surgically intact (two-kidney) rats. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in spontaneously hypertensive rats after either uninephrectomy or uninephrectomy with contralateral renal denervation.

2. Fourteen days after uninephrectomy pair-fed rats were injected for 14 days with cyclosporin A (25 mg/kg body weight) via the subcutaneous route and with nifedipine (0.1 mg/kg body weight) via the intraperitoneal route. Renal and systemic haemodynamics were measured in conscious unrestrained rats.

3. Whole-blood levels of cyclosporin A did not differ between groups (overall 352 ± 22 ng/ml, means ± sem). After uninephrectomy, cyclosporin A decreased the glomerular filtration rate (olive oil versus cyclosporin A: 0.96 ± 0.04 versus 0.70 ± 0.06 ml min−1 100 g body weight, P < 0.02) and effective renal plasma flow (1.94 ± 0.10 versus 1.38 ± 0.13, P < 0.01), and increased renal vascular resistance {(20.2 ± 1.8) × 104 versus (31.6 ± 3.3) × 104 kPa l−1 s [(20.2 ± 1.8) × 103 versus (31.6 ± 3.3) × 103 dyn s cm−5], P < 0.02} and mean arterial pressure (146.7 ± 6.7 versus 167.3 ± 2.9 mmHg, P < 0.05). Neither renal denervation nor nifedipine prevented the reduction in glomerular filtration rate or effective renal plasma flow induced by cyclosporin A.

4. This study infers that the sympathetic nervous system does not play an active role in cyclosporin A nephrotoxicity and demonstrates that the concomitant administration of nifedipine to rats with reduced renal mass does not ameliorate cyclosporin A-induced renal impairment.
Effects of diuretics on stroke development in Kyoto–Wistar stroke-prone spontaneously hypertensive rats
Authors: Smeda John S. , Tkachenko Olexa
Published: August 2015

1. Previous studies have indicated that increases in dietary K+ promote diuresis and retard stroke development in stroke-prone spontaneously hypertensive rats (spSHR) fed a Japanese-style diet containing 4% NaCl.

2. It is possible that elevations in dietary K+ retard stroke development by inducing natriuresis and facilitating the clearance of Na+, and that diuretics associated with natriuresis might also be capable of retarding stroke development in spSHR. To test if this was the case, the onset of stroke development in spSHR fed a low (0.75%) K+ diet containing 4% NaCl (controls) was monitored and compared with that in spSHR treated with (a) frusemide, (b) chlorothiazide, (c) amiloride or (d) acetazolamide, and with (e) untreated spSHR fed a high (2.11%) K+ diet.

3. The onset of stroke, as well as death resulting from stroke, occurred at a significantly later age in spSHR fed a high K+ diet than in spSHR fed a low-K+ diet, despite the fact that both groups of spSHR rats had comparable blood pressures.

4. Treatment of spSHR with the above-named diuretics before stroke development did not alter the blood pressure of the rats. The onset of stroke development and death in spSHR treated with chlorothiazide, amiloride or acetazolamide was comparable with that observed in untreated control spSHR. In spSHR treated with frusemide, the onset of stroke was comparable with that of untreated control spSHR, whereas the onset of death after stroke development was accelerated.

5. Post mortems performed on spSHR that developed stroke indicated the presence of haemorrhagic stroke of comparable severity in the six groups of spSHR studied.

6. The results indicate that treatment of spSHR with diuretics at levels which do not alter the animals’ blood pressure does not alter the timing or incidence of stroke development, and does not prolong the lifespan of the animals after stroke has developed.
Plasma ascorbate levels and inhibition of the antioxidant activity of caeruloplasmin
Authors: Gutteridge John M. C.
Published: August 2015

1. The copper-containing protein caeruloplasmin has several oxidase activities.

2. Its ability to catalyse the oxidation of ferrous ions to the ferric state (ferroxidase activity) makes it an important antioxidant in vivo.

3. Recent reports have suggested that oral supplementation with vitamin C can inhibit the oxidase activities of caeruloplasmin.

4. As expected, damage to DNA and membrane lipids was stimulated by mixtures of iron salt and ascorbate, and this damage could be inhibited by caeruloplasmin provided the molar ratio of ascorbate to caeruloplasmin was kept sufficiently low.

5. When the molar ratio of ascorbate to caeruloplasmin was greater than 200 substantial loss of ferroxidase antioxidant activity occurred.

6. It is unlikely, however, that oral supplementation with vitamin C can raise plasma levels sufficiently to inhibit caeruloplasmin activity in vivo.
Zinc improves the filterability of sickle erythrocytes at intermediate oxygen partial pressures
Authors: Taylor J. A. , Acharya J. , Pearson T. C. , Thompson R. P. H.
Published: August 2015

1. The deformability of erythrocytes from patients with sickle-cell anaemia was measured with a St George's blood filtrometer at a range of oxygen partial pressures and at four levels of zinc loading.

2. When incubated in buffered saline containing zinc and the chelator ethyl maltol, erythrocytes rapidly accumulated zinc and thus their oxygen affinity was increased.

3. Neither the oxygen partial pressure nor zinc loading affected the filtration of normal erythrocytes.

4. Deoxygenation of sickle erythrocytes greatly impaired filtration, although the initial filtration rate declined sharply at different oxygen partial pressures (between 70 and 35 mmHg) in different patients.

5. Low levels of zinc (0.03 ± 0.003 mol of zinc/mol of haemoglobin tetramer) were without effect on sickle cells, but at zinc/haemoglobin ratios of 0.6:1 and above, the sharp fall in filtration rate occurred at oxygen partial pressures 8–25 mmHg below the oxygen partial pressure that impaired filtration of untreated cells.

6. Hence, the deformability of sickle erythrocytes in vitro can be improved by increasing the intracellular content of zinc to 20-fold above normal. Further studies are now required to examine the stability of zinc in erythrocytes, the effects of high intracellular zinc concentrations on erythrocyte viability, and the toxicity of zinc released from zinc-laden cells.
Changes in blood pressure during the normal menstrual cycle
Authors: Dunne F. P. , Barry D. G. , Ferriss J. B. , Grealy G. , Murphy D.
Published: August 2015

1. Changes in blood pressure during the normal menstrual cycle are not well documented, and previous studies have given conflicting results.

2. Thirty normotensive women and ten mildly hypertensive women measured their blood pressure at home each morning for 6 weeks, under standardized conditions, using a UA-751 semi-automatic sphygmomanometer. All had normal menstrual cycles and subjects entered the study at difference phases of the cycle.

3. Blood pressure was higher at the onset of menstruation than at most other phases of the cycle (systolic blood pressure, P < 0.05; diastolic blood pressure, P < 0.001). Adjusted diastolic blood pressure was higher in the follicular than in the luteal phase (mean difference 1.23 mmHg, P < 0.001). Similarly, blood pressure was lower during days 17–26 than during the remainder of the cycle (adjusted mean difference in systolic blood pressure −0.65 mmHg, P = 0.07; adjusted mean difference in diastolic blood pressure − 1.19 mmHg, P < 0.001).

4. Similar patterns were seen in normotensive and hypertensive subjects, and changes in plasma 17β-oestradiol and progesterone concentrations were also similar in the two groups.
Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the renin-aldosterone system
Authors: Cuneo Ross C. , Salomon Franco , Wilmshurst Peter , Byrne Chris , Wiles C. Mark , Hesp Richard , Sönksen Peter H.
Published: August 2015

1. In adult humans with growth hormone deficiency, treatment with growth hormone has recently been shown to have major anabolic effects and to improve exercise performance. The cardiovascular effects of growth hormone in adults with growth hormone deficiency were examined in 24 patients treated with recombinant human growth hormone (0.07 units/kg at night) in a double-blind, placebo-controlled trial lasting 6 months.

2. Compared with placebo, resting M-mode echocardiography showed increases in left ventricular end-diastolic dimension and stroke volume in the group treated with recombinant human growth hormone. No differences were noted between the groups with respect to left ventricular end-systolic dimension, fractional shortening, wall thicknesses or mean arterial blood pressure. Left ventricular myocardial mass increased in the group given recombinant human growth hormone.

3. The supine plasma renin activity was increased and remained elevated over the 6 months, whereas the plasma aldosterone concentration was unchanged, after treatment with recombinant human growth hormone. Clinical signs of sodium retention were evident during the first 3 months of treatment with recombinant human growth hormone.

4. We conclude that treatment with recombinant human growth hormone in adults with growth hormone deficiency resulted in small increases in left ventricular pre-load, due to the sodium-retaining action of growth hormone. Activation of the renin-aldosterone system was involved in such changes. Myocardial hypertrophy was observed without changes in mean arterial pressure, reflecting the anabolic action of growth hormone.
Whole-body and tissue protein synthesis during brief and prolonged fasting in the rat
Authors: Cherel Yves , Attaix Didier , Rosolowska-Huszcz Danuta , Belkhou Rajae , Robin Jean-Patrice , Arnal Maurice , Maho Yvon Le
Published: August 2015

1. Little information is currently available on protein turnover during chronic protein loss situations. We have thus measured the whole-body and tissue protein fractional synthesis rates (ks), the whole-body fractional protein degradation rate (kd), the capacity for protein synthesis (Cs) and the efficiency of protein synthesis (kRNA) in vivo in fed and fasted (1, 5 and about 9 days) 400 g rats.

2. One day of starvation resulted in a reduced ks and an increased kd in the whole body. ks was selectively depressed in skeletal muscles, mainly owing to a reduced kRNA, and was not modified in heart, liver and skin. The contribution of skin to whole-body protein synthesis increased by 39%.

3. During the phase of protein sparing (5 days of fasting), kd in the whole body decreased below the control fed level. ks in skeletal muscles was sustained because kRNA was restored to 82–98% of the control value.

4. Rats were in a protein-wasting phase after 9 days of starvation. kd in the whole body did not increase and was actually 78% of the value observed in fed animals. By contrast, ks in the whole body and tissues decreased to 14–34% of the control values, owing to reductions in both Cs and kRNA. Whatever the duration of the fast, the contribution of the skin to whole-body protein synthesis largely exceeded that of skeletal muscle.

5. The present findings suggest that the main goal in the treatment of chronic protein loss should be to sustain protein synthesis. Our data also emphasize the importance of skin in whole-body protein synthesis in fasting and possibly in other protein loss situations.
ATP production in isolated muscle mitochondria from haemodialysis patients: effects of correction of anaemia with erythropoietin
Authors: Bárány Peter , Wibom Rolf , Hultman Eric , Bergström Jonas
Published: August 2015

1. The ATP production rate in isolated skeletal muscle mitochondria was measured with a bioluminescence method, before and during erythropoietin treatment, in 21 anaemic haemodialysis patients. In addition, the concentrations of ATP, phosphocreatine and total creatine and the ratio of alkali-soluble protein to DNA were determined in skeletal muscle. Maximal oxygen uptake and maximal exercise capacity were determined on a bicycle ergometer.

2. The results unexpectedly showed a 35% higher mitochondrial ATP production rate in the patients before erythropoietin treatment than in sedentary control subjects. On the other hand, mitochondrial density, as measured by the activity of the matrix enzyme glutamate dehydrogenase, was the same in the patients as in the sedentary control group. After 1 year on maintenance erythropoietin treatment, the ATP production rate per kg of muscle decreased in five out of seven patients and reached the same level as in the sedentary control subjects. The ratio between ATP production rate and glutamate dehydrogenase activity was on average 40% higher in the patients at the start and decreased towards the control level in six out of seven patients after 1 year on maintenance erythropoietin treatment. When related to the mitochondrial protein content, a significant reduction in the ATP production rate was observed.

3. The ratio of alkali-soluble protein to DNA in skeletal muscle and the concentrations of ATP, phosphocreatine and total creatine in skeletal muscle at rest were normal in the patients and did not change during the study. The maximal aerobic power improved by 25% after the correction of anaemia.

4. These results suggest that the enhanced mitochondrial ATP production rate in renal anaemia is a metabolic adaptation to decreased oxygen transport and is reversed by long-term correction of anaemia.
Feedback inhibition of insulin secretion in type 2 diabetes
Authors: Baynes C. , Anyaoku V. , Johnston D. G. , Elkeles R. S.
Published: August 2015

1. The purpose of the present study was to examine the ability of insulin to inhibit its own secretion in type 2 diabetes independently of the prevailing plasma glucose concentration.

2. The responses of the plasma C-peptide concentration to sustained hyperinsulinaemia were assessed during a 200 min isoglycaemic clamp study in 14 patients with type 2 diabetes and seven age-and weight-matched control subjects. The arterialized venous plasma glucose concentration was clamped at ∼ 0.3 mmol/l below each subject's own basal level and was not permitted to rise above the basal level.

3. In the fasting state, the plasma C-peptide concentration was slightly, but not significantly, higher in the diabetic patients than in the control subjects (667 versus 413 pmol/l, respectively, P = 0.07), but it remained significantly higher in the diabetic patients during the clamp studies in absolute terms (minimum plasma C-peptide concentration 400 pmol/l in diabetic patients versus 151 pmol/l in control subjects, P <0.05) and was suppressed to a lesser extent when expressed as a percentage change from basal (35.8% in diabetic patients versus 59.4% in control subjects, P <0.01).

4. In order to investigate whether a high plasma glucose concentration was maintaining the plasma C-peptide concentration in the diabetic patients, six of these patients underwent a second clamp study at euglycaemia (plasma glucose concentration 5.2 mmol/l). Under these conditions, the plasma C-peptide concentration was suppressed to the same extent as in the control subjects (from 623 to 195 pmol/l, a change of 62.7%).

5. The results suggest that the insulin-β feedback loop is intact in type 2 diabetes when euglycaemia is acutely restored, but that basal hyperglycaemia maintains elevated insulin secretion rates and may, therefore, blunt the ability of insulin to regulate its own secretion in this condition.
Dilator actions of arginine in human peripheral vasculature
Authors: Calver Alison , Collier Joe , Vallance Patrick
Published: August 2015

1. l-Arginine is the physiological precursor for the formation of endothelium-derived nitric oxide. The synthesis of nitric oxide is stereospecific: d-arginine is not a substrate for nitric oxide synthase. It is possible that the provision of excess l-arginine substrate might increase the vascular synthesis of nitric oxide. We have examined this possibility by studying the effects of local infusion of l-and d-arginine in the forearm resistance bed and the superficial dorsal hand veins of healthy subjects.

2. Drugs were either infused locally into a vein on the back of the hand and then the vein diameter was measured using a linear displacement technique, or into the brachial artery and then the forearm blood flow was measured by venous occlusion plethysmography.

3. In the superficial hand veins, l- and d-arginine free base and l- and d-arginine hydrochloride (all four preparations at a dose of 5 μmol/min) all caused a significant increase in venous diameter. The responses of the l-and d-enantiomers did not differ significantly from one another.

4. In the forearm resistance bed, l- and d-arginine free base and l-arginine hydrochloride were without effect at doses of 10 and 40 μmol/min. However, at doses of 160 μmol/min all three preparations of arginine caused a significant increase in forearm blood flow compared with control values. The responses to the three preparations of arginine did not differ significantly from one another.

5. These results show that arginine in high dose is a vasodilator in both human resistance vessels and superficial veins in vivo. The response to arginine was not stereospecific: both the l- and d-enantiomers had the same effect. The dilator effect of high-dose arginine showed neither arterio-nor veno-selectivity.

6. This suggests that the hypotensive effect of systemic infusions of l-arginine in man is mediated by peripheral vasodilatation. It is not possible to ascribe the actions of arginine supplementation in this study to activation of the l-arginine/nitric oxide pathway through the provision of excess substrate.
Effects of l-arginine on systemic and renal haemodynamics in conscious dogs
Authors: Murakami Marohito , Suzuki Hiromichi , Ichihara Atsuhiro , Naitoh Mareo , Nakamoto Hidetomo , Saruta Takao
Published: August 2015

1. The effects of l-arginine on systemic and renal haemodynamics were investigated in conscious dogs. l-Arginine was administered intravenously at doses of 15 and 75 μmol min−1 kg−1 for 20 min.

2. Mean arterial blood pressure, heart rate and cardiac output were not changed significantly by l-arginine infusion. However, l-arginine infusion induced a significant elevation of renal blood flow from 50 ± 3 to 94 ± 12 ml/min (means ± sem, P < 0.01).

3. Simultaneous infusion of NG-monomethyl-l-arginine (0.5 μmol min−1 kg−1) significantly inhibited the increase in renal blood flow produced by l-arginine (15 μmol min−1 kg−1) without significant changes in mean arterial blood pressure or heart rate.

4. Pretreatment with atropine completely inhibited the l-arginine-induced increase in renal blood flow, whereas pretreatment with indomethacin attenuated it (63 ± 4 versus 82 ± 10 ml/min, P < 0.05).

5. A continuous infusion of l-arginine increased renal blood flow in the intact kidney (55 ± 3 versus 85 ± 9 ml/min, P < 0.05), but not in the contralateral denervated kidney (58 ± 3 versus 56 ± 4 ml/min, P > 0.05).

6. These results suggest that intravenously administered l-arginine produces an elevation of renal blood flow, which may be mediated by facilitation of endogenous acetylcholine-induced release of endothelium-derived relaxing factor and vasodilatory prostaglandins.
Fat-cell heat production, adipose tissue fatty acids, lipoprotein lipase activity and plasma lipoproteins in adiposis dolorosa
Authors: Fagher Birger , Monti Mario , Nilsson-Ehle Peter , Åukesson Björn
Published: August 2015

1. Gluteal adipose tissue was examined in 13 patients with generalized adiposis dolorosa, a clinical condition characterized by painful adiposity with a chronic intractable course. The total metabolic activity of fat cells, isolated by collagenase and suspended in Krebs-Ringer bicarbonate buffer with glucose and insulin, was assessed by the measurement of heat production at 37°C using microcalorimetry.

2. Fat cells were markedly enlarged; their metabolic activity expressed in terms of μW/g, but not in pW/cell, was significantly decreased when compared with both lean and weight-matched non-painful subjects. Both mean values were, however, significantly higher than in grossly obese subjects with similar mean cell size. Heat production as expressed per g of tissue, but not per cell, was inversely correlated with body mass index. One additional patient had unilateral disease, and fat cells from the painful side had a lower heat production than cells from the unaffected side.

3. The fatty acid composition of adipose tissue, as determined by g.c., revealed a significantly increased proportion of monounsaturated (18:1 and 16:1) at the expense of saturated (14:0 and 18:0) fatty acids compared with healthy control subjects. The activity of adipose tissue lipoprotein lipase was slightly, but not significantly, decreased.

4. It is concluded that a metabolic pathogenetic factor cannot be ruled out in adiposis dolorosa. As the results do not explain the nature of the diffuse pain, further studies need to be performed.
Amiloride-sensitive lithium reabsorption during doxazosin-induced blood pressure reduction in rats
Authors: Petersen Jørgen Søberg , Shalmi Michael , Bak Martin , Lomholt Niels , Christensen Sten
Published: August 2015

1. The effects of acute systemic α1-anoceptor blockade by doxazosin on glomerular filtration rate, urine flow, sodium clearance and lithium clearance were investigated in acutely prepared conscious rats.

2. Clearance experiments were performed during water diuresis (20 mmol/l NaCl and 110 mmol/l glucose, 3 ml/h). After a control period, animals were randomized to one of the following treatments: time-control (n = 9), doxazosin (50 μg primer; 30 μg h−1 kg−1) (n = 10), amiloride (1 mg primer; 2.4 mg h−1 kg−1) (n = 10) and doxazosin plus amiloride (n = 9).

3. Doxazosin reduced the mean arterial blood pressure from 125 to 108 mmHg; this was associated with transient reductions in glomerular filtration rate, urine flow and lithium clearance. After the transient anti-diuresis, the sodium excretion rate remained reduced in doxazosin-infused animals. Amiloride increased the sodium excretion rate without having effects on other variables. When doxazosin was given together with amiloride, the reduction in lithium clearance observed during the transient reduction in glomerular filtration rate and urine flow, was partly abolished. Thus the fractional lithium excretion was transiently increased in rats given doxazosin plus amiloride (from 29 to 40%), whereas in rats given doxazosin alone a non-significant reduction was observed (from 28 to 25%). The dissociation between lithium clearance and fractional lithium excretion in the two doxazosin-infused groups was only significant during the transient reduction in glomerular filtration rate and urine flow.

4. The results provide evidence for an amiloride-sensitive lithium reabsorption during acute systemic α1-adrenoceptor blockade. It is suggested that activation of baroreflexes during the acute reduction in mean arterial blood pressure is responsible for stimulation of distal lithium reabsorption by an unknown mechanism.