bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue zinc status and drug elimination in patients with chronic liver disease
Authors: Barry Michael , Keeling P. W. N. , Feely John 
Published: August 2015

1. The zinc status and drug-metabolizing ability of 15 patients with histologically diagnosed hepatic cirrhosis were studied. Zinc status was assessed using both serum and leucocyte zinc concentrations, and drug-metabolizing ability was assessed by antipyrine kinetics.
2. Patients with cirrhosis were found to have lower serum and leucocyte zinc concentrations when compared with a healthy control group.
3. Leucocyte zinc content and antipyrine clearance were correlated. Those patients with the lowest leucocyte zinc content had the greatest impairment of drug metabolism. Antipyrine elimination and serum zinc concentrations were not correlated.
4. Leucocyte zinc concentrations and antipyrine clearance were not influenced by the severity of liver dysfunction, as assessed by using the Child Turcotte classification.
5. These results suggest that tissue zinc depletion in some patients with hepatic cirrhosis may explain in part the impaired capacity to metabolize drugs.
Microheterogeneity of α1-antichymotrypsin in the management of giant-cell arteritis and polymyalgia rheumatica
Authors: Hachulla Eric , Laine Anne , Hayem Annette 
Published: August 2015

1. Using crossed immunoaffinity electrophoresis with free concanavalin A in the first dimension, we studied the glycan microheterogeneity of α1-antichymotrypsin in sera from patients with giant-cell arteritis and/or polymyalgia rheumatica, and its variation in the serum of several of these patients during induction of disease remission by prednisone therapy and possible further recurrence of giant-cell arteritis and/or polymyalgia rheumatica.
2. In the serum of patients with active disease we observed increased proportions of concanavalin A non-reactive and concanavalin A weakly reactive fractions. The results were expressed as the ratio of concanavalin A non-reactive fraction plus concanavalin A weakly reactive fraction to concanavalin A reactive fraction, called Rα1-ACT. An Rα1-ACT higher than 1.8 (upper normal value) was found in 30/31 sera from patients with active disease (sensitivity 97%) and in 2/22 sera from patients with inactive disease (specificity 91%).
3. The erythrocyte sedimentation rate and the serum C-reactive protein level, common markers of biological inflammation, are usually elevated in active giant-cell arteritis and/or polymyalgia rheumatica. The two parameters are commonly used to guide the therapy during the course of the disease, but they have no specificity. An erythrocyte sedimentation rate of greater than 30 mm/h was found in 30/31 sera from patients with active disease (sensitivity 97%) and in 5/22 sera from patients with inactive disease (specificity 77%). Our results show that α1-antichymotrypsin microheterogeneity provides a precise marker of giant-cell arteritis and/or polymyalgia rheumatica activity, particularly when the serum C-reactive protein level is normal or when the erythrocyte sedimentation rate is still high in treated patients. We found a better positive prediction value for Rα1-ACT than for erythrocyte sedimentation rate (94% and 86%, respectively). By determining the Rα1-ACT it is thus possible to follow the exacerbation of the disease when the dose of prednisone is tapered.
4. The correlation coefficients between clinical symptoms, erythrocyte sedimentation rate, levels of C-reactive protein or α1-antichymotrypsin, and Rα1-ACT values were determined. The highest correlation occurred between Rα1-ACT and erythrocyte sedimentation rate (r = 0.57, P &lt;0.0001).
5. Three case reports illustrated the value of determining Rα1-ACT as a useful adjunct test for the diagnosis of giant-cell arteritis and/or polymyalgia rheumatica.
Renal functional reserve in patients with essential hypertension: Effect of inhibition of the renin-angiotensin system
Authors: Valvo Enrico , Casagrande Patrizia , Bedogna Valeria , Dal Santo Francesca , Alberti Daniele , Fontanarosa Cristina , Braggio Paolo , Maschio Giuseppe 
Published: August 2015

1. Urinary albumin excretion and the effect of an acute oral protein load (a meat meal) on glomerular filtration rate ('renal functional reserve') were evaluated in 15 essential hypertensive patients with preserved renal function and compared with 12 normal subjects.
2. Seven patients had microalbuminuria (&gt;30 mg/day) that was not correlated with blood pressure values.
3. After an oral protein load, an average increase of 20% in glomerular filtration rate (from 91 ± 19 to 110 ± 27 ml min−1 1.73 m−2) was found in the hypertensive patients. This change was not statistically different from that observed in normal controls (from 102 ± 7 to 124 ± 9 ml min−1 1.73 m−2). The glomerular response in hypertensive patients was independent of age, duration of hypertension, blood pressure, plasma renin activity, urinary albumin excretion and retinal vascular alterations.
4. All patients were re-evaluated after 6 weeks treatment with a new orally active angiotensin-converting enzyme inhibitor, benazepril. Systolic, diastolic and mean blood pressures were lowered in all the patients, but the drug did not affect the glomerular response to acute protein ingestion or the magnitude of urinary albumin excretion.
5. The findings of a normal ‘renal functional reserve’ and a lack of change in both urinary albumin excretion and the glomerular response after angiotensin-converting enzyme inhibition cast doubt on the existence of increased intraglomerular pressure in hypertensive patients.
Skeletal muscle and whole-body protein turnover in cirrhosis
Authors: Morrison W. L. , Bouchier I. A. D. , Gibson J. N. A. , Rennie M. J. 
Published: August 2015

1. We investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indices of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with cirrhosis and in 11 healthy control subjects. Whole-body protein turnover was also measured using l-[1-13C]leucine.
2. Leg efflux of tyrosine was 45% greater in cirrhotic patients than in normal control subjects [−6.5(1.4 to −19.1) vs −4.2 (−2.2 to −7.7) μmol min−1 100 mg−1 of leg, median (range), P &lt;0.025]. 3-Methylhistidine efflux was not significantly altered.
3. In cirrhosis, whole-body leucine flux was normal but whole-body leucine oxidation was elevated so that whole-body protein synthesis was depressed by 17%.
4. The results indicate the predominant mechanism of muscle wasting in cirrhosis to be a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.
Cutaneous Vascular Responses Evoked in the Hand by the Cold Pressor Test and by Mental Arithmetic
Authors: Marriott I. , Marshall Janice M. , Johns E. J. 
Published: August 2015

1. Laser Doppler flowmetry has been used to study changes in cutaneous erythrocyte flux produced in the hand (i) on successive immersion of the contralateral hand in water at 20°C (cold test) and then in water at 0–4°C (cold pressor test), and (ii) by mental arithmetic.
2. In 11 subjects, placing the right hand in water at 20°C for 2 min induced a significant decrease in cutaneous erythrocyte flux in the contralateral hand and a significant fall in mean arterial pressure. Cutaneous vascular resistance, calculated as arterial pressure/cutaneous erythrocyte flux, showed no significant change. Thus, the decrease in erythrocyte flux was apparently due to a fall in perfusion pressure.
3. Subsequent immersion of the right hand in water at 0–4°C for 2 min caused a significant decrease in erythrocyte flux in the contralateral hand and a significant rise in mean arterial pressure. It is concluded that the cold pressor response evoked from one hand elicited a substantial reflex vasoconstriction in the skin of the other hand; accordingly, calculated cutaneous vascular resistance increased significantly.
4. Eight subjects performed mental arithmetic for two periods of 2 min separated by a rest period of 2 min. By the end of the second minute of each period of mental arithmetic there was a significant decrease in erythrocyte flux. Mean arterial pressure increased significantly in the first period only, but calculated cutaneous vascular resistance increased in both periods, consistent with cutaneous vasoconstriction.
5. The cold pressor test and mental arithmetic are aversive stimuli that evoke the characteristic pattern of the alerting or defence response which includes splanchnic vasoconstriction and muscle vasodilatation. Previous studies on the cutaneous vascular component of this response have yielded equivocal results. The present study provides firm evidence that it includes cutaneous vasoconstriction, at least in the hand.
Effect of Atrial Natriuretic Factor on Bronchomotor Tone in the Normal Human Airway
Authors: Hulks G. , Jardine A. G. , Connell J. M. C. , Thomson N. C. 
Published: August 2015

1. Asthmatic patients bronchodilate in response to infused atrial natriuretic factor. We wished to determine whether the airways of normal subjects responded in a similar way.
2. Changes in airway resistance, as determined by specific airway conductance, were measured in eight normal subjects in response to intravenous infusion of atrial natriuretic factor at doses of 0.5, 2 and 10 pmol rnin−1 kg−1.
3. No significant effect was observed on specific airway conductance at any rate of infusion despite maximum mean (sem) plasma levels of 597 (62) pg of atrial natriuretic factor/ml in peripheral venous blood.
4. A second study was performed using six of the eight original subjects and employing a pharmacological dose of 50 pmol of atrial natriuretic factor min−1 kg−1. This produced mean plasma levels of 2056 pg/ml and a mean increase of 31% in specific airway conductance.
5. It is concluded that pharmacological, but not pathophysiological, elevations of plasma atrial natriuretic factor may significantly alter bronchomotor tone in normal subjects.
Orthostatic Circulatory Control in the Elderly Evaluated by Non-Invasive Continuous Blood Pressure Measurement
Authors: Imholz B. P. M. , Dambrink J. H. A. , Karemaker J. M. , Wieling W. 
Published: August 2015

1. Continuous orthostatic responses of blood pressure and heart rate were measured in 40 healthy and active elderly subjects over 70 years of age in order to assess the time course and rapidity of orthostatic cardiovascular adaptation in old age.
2. During the first 30 s (initial phase) the effects of active standing and passive head-up tilt closely resembled those observed earlier in younger age groups. Standing up was accompanied by a drop (mean ± SD) in systolic and diastolic blood pressures of 26 ± 13 mmHg and 12 ± 18 mmHg, respectively, at around 10 s, and a subsequent rise up to 11 ± 17 mmHg and 8 ± 6 mmHg above supine values at around 20 s. The drop in blood pressure upon standing was accompanied by a transient increase in heart rate with a maximum of 13 beats/min, followed by a gradual decrease to 7 beats/min above supine levels. These characteristic transient changes were absent upon a passive head-up tilt.
3. After 1–2 min of standing (early steady-state phase) diastolic blood pressure and heart rate increased significantly after active and passive postural changes. On average, for all subjects systolic blood pressure tended to increase from control during 5–10 min standing, reaching a significant difference at 10 min. During standing, the largest increases in systolic blood pressure were found in subjects with the lowest supine blood pressures.
4. In conclusion, for the investigation of orthostatic circulatory responses in elderly subjects the following factors have to be taken into account: active versus passive changes in posture, the timing of the blood pressure reading, and the level of supine blood pressure.
Effects of Lead and a Low-Molecular-Weight Endogenous Plasma Inhibitor on the Kinetics of Sodium—Potassium-Activated Adenosine Triphosphatase and Potassium-Activated p-Nitrophenylphosphatase
Authors: Weiler Elmar , Khalil-Manesh Farhad , Gonick Harvey C. 
Published: August 2015

1. Lead, ouabain and an endogenous plasma inhibitor were all found to be potent inhibitors of purified hog cerebral cortex sodium—potassium-activated adenosine triphosphatase and potassium-stimulated p-nitrophenylphosphatase.
2. The kinetic characteristics of inhibition of both enzymes by lead and the endogenous plasma inhibitor differed in several respects. For sodium—potassium-activated adenosine triphosphatase, lead and the endogenous plasma inhibitor were non-competitive inhibitors with respect to potassium; lead was competitive with respect to sodium, whereas the endogenous plasma inhibitor had no effect; lead was competitive with respect to magnesium adenosine triphosphate, whereas the endogenous plasma inhibitor was uncompetitive. For potassium-activated p-nitrophenylphosphatase, both lead and the endogenous plasma inhibitor were competitive with respect to potassium; lead showed a mixed type of inhibition with respect to p-nitrophenylphosphate, whereas the endogenous plasma inhibitor was non-competitive.
3. Lead and the endogenous plasma inhibitor exhibited synergistic inhibitory activity on sodium—potassium-activated adenosine triphosphatase.
4. These results suggest that lead could play a contributory role in the pathogenesis of essential hypertension via an additive inhibition of vascular smooth muscle sodium—potassium-activated adenosine triphosphatase.
Effect of Endothelin on the Function of the Isolated Perfused Working Rat Heart
Authors: Firth J. D. , Roberts A. F. C. , Raine A. E. G. 
Published: August 2015

1. The effect of endothelin on the performance of the isolated perfused working rat heart has been examined.
2. A low concentration of endothelin (60 pmol/l) produced a gradual but sustained increase in cardiac output; coronary vascular resistance was unaffected.
3. A high concentration of endothelin (600 pmol/l) produced a rapid increase in cardiac output, followed by a marked fall in cardiac output as progressive, severe coronary vasoconstriction developed.
4. The coronary vasoconstriction induced by endothelin (600 pmol/l) was partially blocked by nicardipine (0.5 pmol/l)
5. In the presence of either nicardipine (0.5 μmol/l) or verapamil (0.2 μmol/l), the increment in cardiac output induced by endothelin (600 pmol/l) was greater than that induced by the addition of the same concentration of endothelin to hearts which had not been exposed to calcium-entry blockers.
6. The effect of endothelin on myocardial contractility has a different time course, concentration dependence and response to calcium-entry blockade than the effect on the coronary vasculature. This suggests that different mechanisms are involved in the generation of the myocardial and vascular responses to endothelin.
Metabolism of 15N-Labelled Urea in the Functioning and Defunctioned Human Colon
Authors: Moran B. J. , Jackson A. A. 
Published: August 2015

1. The luminal metabolism of urea was studied using double-labelled urea ([15N2]urea) which was placed in the lumen of the colon through a colostomy. The recovery of label was measured as [15N2]urea or [14N,15N]urea in urine and as 15N in stool.
2. Five patients with a loop colostomy allowed a comparison of the right functioning colon with the left defunctioned colon in the same individual. Five subjects with a left end-colostomy enabled a comparison of the right with the left functioning colon.
3. A significantly greater proportion of labelled urea was recovered as [15N2]urea in the urine when the dose was placed in the left defunctioned colon (29%) compared with either the left or the right functioning colon (9 and 4%, respectively). This is interpreted as being a result of a decrease in the bacterial activity and concomitant urea hydrolysis in the defunctioned colon.
4. On average more than half of the label was retained in the body, regardless of whether the urea was placed in the functioning or the defunctioned colon, on the left or on the right.
5. The data confirm that the colon is permeable to the intact urea molecule. Intraluminal urea is readily hydrolysed in the functioning colon. A large proportion of the nitrogen released by urea hydrolysis may be retained within the metabolic nitrogen pool of the host. There are significant differences in the handling of urea nitrogen in the defunctioned colon relative to the functioning colon.
Effect of Amiodarone on erythrocyte Shape and Membrane Properties
Authors: Reinhart W. H. , Rohner F. 
Published: August 2015

1. Amiodarone is a potent anti-arrhythmic drug with lipophilic properties. The intercalation of such a drug into the membrane of erythrocytes may alter their shape and have an impact on the flow properties of blood. We therefore studied the influence of amiodarone on erythrocyte shape and deformability in vitro and in vivo.
2. Incubation in vitro with increasing amiodarone concentrations led to a progressive stomatocytic shape transformation and a decreased deformability of the erythrocytes.
3. Amiodarone treatment in eight patients did not affect erythrocyte morphology and deformability. However, an increase in the membrane cholesterol/phospholipid ratio was found.
4. The stomatocytic shape transformation of erythrocytes in vitro indicates that amiodarone intercalates in the inner hemileaflet of the lipid bilayer leading to membrane internalization. These results shed light on the interaction of amiodarone with biomembranes.
Platelet Angiotensin II Binding and Plasma Renin Concentration, Plasma Renin Substrate and Plasma Angiotensin II in Human Pregnancy
Authors: Baker Philip N. , Pipkin Fiona Broughton , Symonds E. Malcolm 
Published: August 2015

1. The results are presented of a cross-sectional study of 25 non-pregnant and 125 pregnant/postnatal women in whom platelet angiotensin II binding and plasma angiotensin II, plasma renin concentration and plasma renin substrate were measured.
2. Platelet angiotensin II binding was significantly lower in the first-trimester patients as compared with the non-pregnant women (P &lt; 0.001). Specific binding remained low in the second and third trimesters, and in those patients studied 24 h after delivery. However, higher values, approximating to the non-pregnant level, were found 6 weeks postnatally (n = 25 for each group).
3. Plasma angiotensin II, plasma renin concentration and plasma renin substrate increased in pregnancy, with the increase becoming statistically significant as compared with the non-pregnant women in the second trimester. Maximal median values of plasma angiotensin II and plasma renin substrate were found in the third trimester, but maximal median values of plasma renin concentration were found in the second trimester. The concentrations of all three hormones fell after delivery.
4. There was an inverse correlation between platelet angiotensin II binding and simultaneously measured endogenous levels of plasma angiotensin II (P &lt; 0.02) and plasma renin substrate (P &lt; 0.05) in the 25 non-pregnant subjects. These findings support the concept of the angiotensin II receptor concentration being regulated by the plasma angiotensin II level. There was no correlation between platelet angiotensin II binding and plasma renin concentration.
5. In pregnancy, no correlation between platelet angiotensin II binding and plasma angiotensin II, plasma renin concentration or plasma renin substrate was found. This suggests that any regulation by plasma angiotensin II may not operate in pregnancy, when reduced binding concentrations are present. No statistically significant correlation was found at either 24 h or 6 weeks after delivery.
Metabolic Regulation of Renal Gluconeogenesis in Response to Sepsis in the Rat
Authors: Salleh M. , Ardawi M. , Khoja Samir M. , Newsholme Eric A. 
Published: August 2015

1. The regulation of renal gluconeogenesis was studied in rats made septic by a caecal ligation and puncture technique.
2. Blood glucose concentrations were not markedly different in septic rats, but lactate, pyruvate and alanine concentrations were markedly increased, compared with sham-operated rats. Conversely, blood ketone body concentrations were significantly decreased in septic rats. Both plasma insulin and glucagon concentrations were markedly elevated in response to sepsis.
3. The maximal activities of glucose-6-phosphatase (EC 3.1.3.9), fructose-1,6-bisphosphatase (EC 3.1.3.11), pyruvate carboxylase (EC 6.4.1.1) and phosphoenol-pyruvate carboxykinase (EC 4.1.1.49) were markedly decreased in kidneys obtained from septic rats, suggesting diminished renal gluconeogenesis.
4. Renal concentrations of lactate, pyruvate and other gluconeogenetic intermediates were markedly elevated in septic rats, whereas those of acetyl-CoA and fructose 2,6-bisphosphate were decreased and unchanged, respectively.
5. The rate of gluconeogenesis from added lactate, pyruvate and glycerol was decreased in isolated incubated renal tubules from septic rats.
6. Sepsis decreased the arteriovenous concentration difference for glucose, lactate, and alanine. Septic rats showed decreased net rates of glucose production and net rates of removal of lactate and alanine as compared with sham-operated controls.
7. It is concluded that the diminished capacity for renal gluconeogenesis in septic rats could be the result of changes in the maximal activities or regulation of key non-equilibrium gluconeogenic enzymes or both, but the effect of other factors (e.g. toxins) has not been excluded.
Evidence for Abnormal Na+/H+ Antiport Activity Detected by Phosphorus Nuclear Magnetic Resonance Spectroscopy in Exercising Skeletal Muscle of Patients with Essential Hypertension
Authors: Dudley C. R. K. , Taylor D. J. , Ng L. L. , Kemp G. J. , Ratcliffe P. J. , Radda G. K. , Ledingham J. G. G. 
Published: August 2015

1. Exercise-induced pH changes in skeletal muscle were studied in a group of eight subjects with essential hypertension by using 31P n.m.r. spectroscopy.
2. Leucocyte Na+/H+ antiport activity was measured in vitro in the same subjects using a pH-sensitive fluorescent dye.
3. Resting skeletal muscle pH and unstimulated leucocyte pH values were similar to those in control subjects, but increased Na+/H+ antiport activity was demonstrated in the leucocytes from hypertensive subjects by acid loading in vitro. Decreased skeletal muscle acidification and an increased rate of pH recovery was also demonstrated in vivo in these same patients during an acid load induced by isotonic exercise.
4. These findings suggest that the increased cellular Na+/H+ antiport activity, which has been demonstrated in vitro in essential hypertension, also affects the biochemical response of skeletal muscle to physiological levels of exercise. This strengthens the argument that increased Na+/H+ antiport activity in hypertension is a generalized and physiologically relevant cellular abnormality.