bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of effect of peripheral nervous blockade on nocturnal fluctuations in lower-leg subcutaneous blood flow in man
Authors: Sindrup J. H. , Petersen L. J. , Kastrup J. , Wroblewski H. , Kristensen J. K. 
Published: August 2015

1. The local subcutaneous adipose tissue blood flow was measured simultaneously in the right and left lower legs of 10 normal human subjects under outpatient nocturnal conditions. The 133Xe-wash-out technique, portable CdTe(Cl) detectors and a portable data-storage unit were used for the measurement of blood flow.
2. The purpose of the study was to unveil the possible role of centrally controlled nerve fibres to the measurement area as mediators of a previously described nocturnal subcutaneous hyperaemia of 2 h duration. Therefore, before the sleeping period, a local nervous blockade was applied immediately proximal to the isotope depot on the right lower leg by the injection of approximately 15 ml of bupivacaine (5 mg/ml) subcutaneously.
3. Control experiments revealed blockade of the baroreceptor vasoconstrictor reflex activity 4 h after application of the local nervous blockade in three subjects examined.
4. Identical nocturnal isotope-wash-out curves were recorded from the two legs. Subcutaneous blood flow was found to increase significantly (P &lt;0.0001) after approximately 1 h of sleep and the hyperaemia persisted for 2 h.
5. A significant positive correlation was detected between the latency periods from going to bed until the onset of the hyperaemia in the right and left lower legs (P &lt;0.001, r = 0.95).
6. No significant difference could be detected between the relative blood flow increase during the hyperaemic phase in the right and left lower legs (P = 0.83).
7. It is concluded that the present data seem to rule out a central nervous factor(s) as the eliciting mechanism of the nocturnal subcutaneous hyperaemia. A circulating humoral factor(s) might be involved, although modification by local metabolic factors cannot be excluded. The possible physiological significance of the nocturnal hyperaemia is discussed.
Effect of Posture and Acute Glycaemic Control on the Excretion of Retinol-Binding Protein in Normoalbuminuric Insulin-Dependent Diabetic Patients
Authors: Catalano Carlo , Winocour Peter H. , Gillespie Susan , Gibb Ian , Alberti K. George M. M. 
Published: August 2015

1. It has been suggested that tubular damage may precede gomerular damage at the onset of diabetic nephropathy. This may be reflected by increased urinary excretion of low-molecular-mass proteins, such as retinol-binding protein.
2. We have measured the urinary excretion rate of retinol-binding protein overnight, during orthostasis and during a hyperinsulinaemic euglycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 34 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 10 normal control subjects. Normal control subjects were not clamped. A further four normoalbuminuric insulin-dependent diabetic patients were rendered euglycaemic without a water load.
3. Overnight retinol-binding protein excretion rate was 58 (16-157) [median(range)] ng/min in patients with insulin-dependent diabetes and 32 (15-72) ng/min in control subjects (P &lt; 0.01). The excretion rate did not change during orthostasis [patients with insulin-dependent diabetes, 67 (3-173) ng/min; control subjects, 23 (5-78) ng/min]. During the euglycaemic clamp retinol-binding protein excretion rate increased to 383 (78-4897) ng/min in patients with insulin-dependent diabetes (P &lt; 0.01). An average increment in retinol-binding protein excretion rate of greater than 4000% was noted after acute euglycaemia in those patients with insulin-dependent diabetes who were not water-loaded.
4. In insulin-dependent diabetes, both overnight and orthostatic retinal-binding protein excretion was not correlated with fasting blood glucose concentration, HbA1, fructosamine or duration of diabetes. The absolute and incremental excretion rates of retinol-binding protein during the clamp were, however, correlated with both fasting blood glucose concentration and glucose excretion rate (rs = 0.41-0.48, P &lt; 0.01).
5. The study demonstrates that retinol-binding protein excretion is increased in insulin-dependent diabetes in the absence of microalbuminuria and that this increase in retinol-binding protein excretion is particularly pronounced after acute euglycaemia. Acute tubular dysfunction related to acute changes in glucose control appears to be the most likely explanation, but established tubular damage could also be implicated. Postural variation in retinol-binding protein excretion was not detected.
Enzymuria in Non-Insulin-Dependent Diabetic Patients: Signs of Tubular Cell Dysfunction
Authors: Ikenaga Hideki , Suzuki Hiromichi , Ishii Naohito , Itoh Hajime , Saruta Takao 
Published: August 2015

1. To evaluate tubular damage in diabetic patients, we measured the 24 h urinary excretion of five enzymes (N-acetyl-β-D-glucosaminidase, γ-glutamyl transpeptidase, dipeptidyl aminopeptidase IV, alanine aminopeptidase and alkaline phosphatase) that originate in renal proximal tubular cells.
2. Studies were performed on 118 non-insulin-dependent diabetic patients, 59 non-diabetic patients with chronic renal disease and 47 normal control subjects. First, the correlation between renal function, glycaemic control and urinary enzyme excretion was investigated. Secondly, the subjects were treated by controlled diet therapy to assess the effects of better glycaemic control on urinary enzyme excretion.
3. Regardless of a diabetic or non-diabetic cause of renal dysfunction, all of the five enzymes showed abnormal urinary excretion in patients with renal insufficiency (serum creatinine concentration &lt; 2.0 mg/dl). In diabetic patients, however, an increase in N-acetyl-β-D-glucosaminidase excretion and a decrease in γ-glutamyl transpeptidase excretion were noted even in those who had no signs of renal dysfunction, including microalbuminuria. Moreover, the excretion of these two enzymes had a higher degree of correlation with glycaemic control and renal function than did that of the other three enzymes. Multiple regression analysis revealed that excretion of N-acetyl-β-D-glucosamindase is best correlated with urinary protein (r2 = 0.35), whereas excretion of γ-glutamyl transpeptidase is closely associated with glomerular filtration rate (r2 = 0.33).
4. In diabetic patients, diet therapy improved glycaemic control but had no effects on renal function, microalbumin excretion and β2-microglobulin excretion. In contrast, abnormal N-acetyl-β-D-glucos-aminidase and γ-glutamyl transpeptidase excretion were both significantly improved in diabetic patients without overt renal dysfunction. However, in non-diabetic patients and diabetic patients with renal insufficiency, there were no changes in urinary enzyme excretion.
5. These results suggest that there is reversible tubular damage in the early stages of diabetic nephropathy. Measurement of urinary excretion of N-acetyl-β-D-glucosaminidase and γ-glutamyl transpeptidase may be especially useful in the detection of this tubular dysfunction.
Derivation of Urinary Dopamine from Plasma Dihydroxyphenylalanine in Humans
Authors: Wolfovitz Efrat , Grossman Ehud , Folio Carol J. , Keiser Harry R. , Kopin Irwin J. , Goldstein David S. 
Published: August 2015

1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spillover) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover.
2. L-Dihydroxyphenylalanine (0.33 μg min−1 kg−1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenylacetic acid.
3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 ± (SEM) 0.01 to 0.14 ± 0.03 nmol/min, t = 2.80, P &lt;0.02] and dopamine (from 1.03 ± 0.19 to 1.30 ± 0.28 nmol/min, t = 2.35, P &lt;0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged.
4. Renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounted for virtually all the urinary excretion of endogenous dopamine, but for only a minor portion of the excreted endogenous dihydroxyphenylacetic acid.
5. We conclude that in humans: (1) circulating dihydroxyphenylalanine is the main source of urinary dopamine but only a minor source of urinary dihydroxyphenylacetic acid; and (2) increased spillover of endogenous dihydroxyphenylalanine does not account for the increased excretion of these compounds during salt loading.
Simvastatin and Intracellular pH Regulation by the Na+/H+ Antiport of Sv40-Virus-Transformed Human Mrc5 Fibroblasts
Authors: Davies J. E. , Ng L. L. 
Published: August 2015

1. Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase by simvastatin leads to inhibition of both cell growth and Na+/H+ antiport activity. The effect of simvastatin on intracellular pH and Na+/H+ antiport activity was therefore studied on an adherent cell line, the SV40-virus-transformed MRC5 human fibroblast.
2. Simvastatin led to a dose-dependent decrease in intracellular pH, attributed to a reduction in Na+/H+ exchange, together with a rounding of cell shape. Mevalonate (1 mmol/l) prevented these effects of simvastatin, and when added after inhibition of the antiport by simvastatin, reversed these changes within 1–2 h.
3. The phenomenon of mevalonate reversal of anti-port inhibition by simvastatin was not sensitive to cycloheximide, indicating its post-translational nature. This was also consistent with the short period of incubation with mevalonate leading to reversal of antiport inhibition (1-2h). These changes in intracellular pH regulation were not due to alterations in cell cholesterol content.
4. A variety of inhibitors of post-translational processes, such as N-linked glycosylation (tunicamycin), phosphorylation (staurosporine), isoprenylation (farnesol, limonene), and of pertussis-toxin-sensitive G-proteins or calmodulin (W7), had no effect on the reversal by mevalonate of simvastatin-induced changes in Na+/H+ antiport activity.
5. N-Ethylmaleimide (50 μmol/l for 5 min) prevented mevalonate reversing the effects of simvastatin, suggesting the importance of thiol groups in the phenomenon of reversal of the inhibition of Na+/H+ antiport activity by simvastatin. Furthermore, concurrent incubation of simvastatin-treated cells with dithiothreitol (1 mmol/l) and N-ethylmaleimide restored the ability of mevalonate to reverse the inhibitory effects of simvastatin on Na+H+ antiport activity.
Effect of Tri-Iodothyronine Administration on Skeletal Muscle Intracellular Ph in the Rat
Authors: Thompson C. H. , Anderson Y. , Jagasia D. H. , Radda G. K. , Rajagopalan B. 
Published: August 2015

1. Male Wistar rats were injected with tri-iodothyronine intraperitoneally for either 3 or 5 days.
2. Using 31P nuclear magnetic resonance spectroscopy, skeletal muscle intracellular bioenergetics of the leg were studied at rest and during sciatic nerve stimulation.
3. Tri-iodothyronine caused intracellular alkalinization of the cell, implying that administration of tri-iodothyronine induces an alteration in the set point for the sodium/proton antiport, the chief controller of intracellular pH.
4. During stimulation, there was less acidification of the skeletal muscle cell in the tri-iodothyronine-injected rats, implying either increased intrinsic buffering capacity of the muscle or increased proton efflux possibly due to increased activity of the sodium/proton antiport.
5. Effective proton efflux from the skeletal muscle cell may be sensitive to circulating levels of tri-iodothyronine.
Dose-Response Effects of Adrenergic and Cholinergic Stimulation on Atrial Natriuretic Peptide Secretion from Beating Isolated Guinea-Pig Atria
Authors: Speake P. F. , Pirie S. C. , Kibble J. D. , Muneer A. , Taylor D. , Birring S. , Green R. 
Published: August 2015

1. The possible role of autonomic neurotransmitters in atrial natriuretic peptide secretion was investigated using spontaneously beating guinea-pig atria in vitro. Dose responses were determined for adrenaline, noradrenaline and acetylcholine and the selective α- and β-adrenoceptor agonists phenylephrine and isoprenaline, respectively. Adrenoceptor effects were further studied using the selective α- and β-adrenoceptor antagonists prazosin and propranolol, respectively, in conjunction with maximal adrenaline challenge. Results for rate and force of contraction and atrial natriuretic peptide secretion are expressed as a ratio (mean ± SEM) of a 15 min treatment period (stage 2) to a corresponding pretreatment period (stage 1).
2. Adrenaline and noradrenaline caused dose-dependent increases in the rate and force of contraction and in atrial natriuretic peptide secretion with a peak secretory response at 2 × 10−6 mol/l of 1.54 ± 0.08 (P &lt;0.01) and 1.34 ± 0.08 (P &lt;0.01) for adrenaline and noradrenaline, respectively. Acetylcholine decreased the rate and force of contraction, and ANP secretion was reduced to 0.47 ± 0.06 at 3 × 10−5 mol/l (P &lt;0.01). Isoprenaline increased the rate and force of contraction and atrial natriuretic peptide secretion with a peak secretory response of 152 ± 0.22 at 2 × 10−6 mol/l (P &lt;0.01). Phenylephrine increased the force but had no effect on the rate of contraction, and stimulated atrial natriuretic peptide secretion to 1.13 ± 0.09 at 2 × 10−5 mol/l (P &lt;0.05). After both α- and β-adrenoceptor blockade, adrenaline was still able to significantly stimulate atrial natriuretic peptide secretion and positive inotropy. There was no chronotropic effect of adrenaline in the presence of propranolol. Simultaneous α- and β-adrenoceptor blockade inhibited all the effects of adrenaline.
3. A significant correlation was observed between the absolute change in rate of contraction and the absolute change in atrial natriuretic peptide secretion upon stimulation with each of the drugs (r = 0.63, P &lt; 0.001). A similar relationship between developed tension and atrial natriuretic peptide secretion could not be demonstrated.
4. In conclusion, secretion of atrial natriuretic peptide from guinea-pig atria was stimulated by adrenergic and inhibited by cholinergic agonists. The adrenergic response was mediated by both α- and β-adrenoceptor stimulation. The observed changes in the rate of contraction showed a significant correlation with atrial natriuretic peptide secretion.
Mitogenic Events Induced by Vasopressin in Aortic Fibroblasts from Spontaneously Hypertensive Rats
Authors: Zhu Ding Liang , Herembert Thierry , Marche Pierre 
Published: August 2015

1. To further explore the mechanisms of arterial growth, we investigated the signalling pathways through which arginine-vasopressin acts as a mitogen in cultured adventitial aortic fibroblasts of the spontaneously hypertensive rat, and we examined the mechanisms involved in the hyperresponsiveness to arginine-vasopressin of fibroblasts from spontaneously hypertensive rats compared with fibroblasts from Wistar-Kyoto rats.
2. Arginine-vasopressin-induced [3H]thymidine incorporation was used to determine the peptide mitogenicity. Arginine-vasopressin-triggered hydrolysis of phosphoinositides by phospholipase C was evaluated by measuring [3H]inositol phosphate formation. The role of protein kinase C and protein tyrosine kinases in arginine-vasopressin mitogenicity was assessed by stimulating the cells with arginine-vasopressin in the presence of 12-O-tetradecanoylphorbol 13-acetate and tyrphostin (a tyrosine kinase inhibitor), respectively.
3. Arginine-vasopressin-induced DNA synthesis was completely abolished in confluent cells, whereas [3H]inositol phosphate formation was only reduced. The presence of 12-O-tetradecanoylphorbol 13-acetate markedly decreased arginine-vasopressin-induced [3H]thymidine incorporation in fibroblasts from spontaneously hypertensive rats and was without effect in fibroblasts from Wistar-Kyoto rats. Tyrphostin abolished arginine-vasopressin-induced [3H]thymidine incorporation in a dose-dependent manner and did not affect the formation of inositol phosphates.
4. These results indicate that phospholipase C activation is not sufficient for arginine-vasopressin-induced mitogenesis. They also suggest that (i) tyrosine kinase activation is a necessary step in the transduction of the arginine-vasopressin mitogenic signal, and (ii) protein kinase C participates in the increased mitogenic potency of arginine-vasopressin in spontaneously hypertensive rats.
Venous Blood Arterialization and Parameters from the Minimal Models of Glucose Disappearance and Post-Hepatic Insulin Delivery
Authors: Godsland I. F. , Felton C. , Wynn V. 
Published: August 2015

1. Modelling analysis of intravenous glucose tolerance test glucose and insulin concentrations can provide measures of insulin sensitivity and metabolism from a single straightforward procedure. However, little is known of the effects of blood arterialization on model-derived parameters.
2. Intravenous glucose tolerance tests were carried out on 18 subjects, with measurement of glucose and insulin concentrations in simultaneously sampled non-arterialized and arterialized blood. Blood oxygen saturation, partial pressure of CO2 and pH were measured on both non-arterialized and arterialized blood during the intravenous glucose tolerance test. Using the minimal models of glucose disappearance and post-hepatic insulin delivery, measures of insulin sensitivity, glucose-dependent glucose disposal, firstand second-phase post-hepatic insulin responsiveness to glucose and plasma insulin elimination rate were derived from intravenous glucose tolerance test glucose and insulin concentrations in both arterialized and non-arterialized blood.
3. During the intravenous glucose tolerance test mean blood oxygen saturation was 6.7% higher, partial pressure of CO2 was 0.3 kPa lower and pH was 0.015 higher in arterialized than non-arterialized blood. Mean parameter values did not differ when derived from measurements made on non-arterialized and arterialized blood. Model-derived parameters were not related to the degree of arterialization, although there was some consistent variation with sampling site for parameters of glucose-dependent glucose disposal (Sg), first-phase post-hepatic insulin responsiveness (φ1) and insulin elimination (ni).
4. Measurements made on non-arterialized blood are suitable for analyses employing the minimal models of glucose disappearance and post-hepatic insulin delivery. Imprecision in some parameters may be diminished by adherence to a single sampling site.
Atrial Natriuretic Peptide in the Pericardial Fluid of Patients with Heart Disease
Authors: Amano Jun , Suzuki Akio , Sunamori Makoto , Shichiri Masayoshi , Marumo Fumiaki 
Published: August 2015

1. The pericardial fluid of 20 open heart surgery patients with acquired heart disease was analysed for atrial natriuretic peptide by radioimmunoassay.
2. The concentration of atrial natriuretic peptide in the pericardial fluid was significantly higher than in the corresponding plasma (316.8 ±50.0 versus 121.7 ± 29.1 pg/ml; P &lt;0.01) and was higher in patients with congestive heart failure than in those without heart failure (469.3 ±78.6 versus 181.8 ± 26.7 pg/ml; P &lt;0.001). Pericardial and plasma atrial natriuretic peptide concentrations showed a significant positive correlation. Pericardial fluid and plasma samples were fractionated using both reverse-phase high-performance liquid chromatography and gel permeation chromatography. Each fraction was assayed for atrial natriuretic peptide by radioimmunoassay, revealing the presence of β-atrial natriuretic peptide as well as α- and γ-atrial natriuretic peptide.
3. The pericardial fluid concentration of cyclic GMP, the intracellular second messenger for atrial natriuretic peptide, was significantly higher in patients with congestive heart failure than in patients without heart failure.
Modulation of the Anabolic Effect of Synthetic Human Parathyroid Hormone Fragment-(1-34) in the Bone of Growing Rats by Variations in the Dosage Regimen
Authors: Riond Jean-Luc 
Published: August 2015

1. The influence of the time of the day of the administration of synthetic human parathyroid hormone fragment-(1-34) [hPTH-(1-34)] on its anabolic effect in bone was investigated in 23 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control morning, hPTH-(1-34)-treated morning, vehicle control afternoon and hPTH-(1-34)-treated afternoon, and once daily received a subcutaneous injection of 8 μg of hPTH-(1-34)/100 g body weight for 11 days. The increase in net intestinal calcium absorption and the increase in calcium balance were not influenced by the time of day of hPTH-(1-34) treatment. Four days after cessation of treatment, the net intestinal calcium absorption and calcium balance in hPTH-(1-34)-treated rats were not different from those of the control rats.
2. Modulation of the anabolic effect by variation of the hPTH-(1-34) dosage regimen was investigated in 43 60-day-old female Wistar rats. Rats were randomly assigned to the groups vehicle control, environmental control, 8 μg of hPTH-(1-34)/100 g body weight every 3 days for 24 days, 8 μg of hPTH-(1-34)/100g body weight every 2 days for 16 days, 8 μg of hPTH-(1-34)/100 g body weight every day for 8 days, 4 μg of hPTH-(1-34)/100 g body weight twice a day for 8 days and 2.7 μg of hPTH-(1-34)/100 g body weight three times a day for 8 days. In all cases, the total dose of hPTH-(1-34) received was 64 μg/100g body weight. Net intestinal calcium absorption and calcium balance increased significantly in the groups that received hPTH-(1-34) once a day, twice a day and three times a day. In relation with increased frequency of dosing, a significant linear trend existed for the increase in net intestinal calcium absorption and calcium balance. The hPTH-(1-34)-induced increase in total tibia calcium, total vertebrae calcium, tibia dry weight and vertebrae dry weight also tended to be more pronounced with more frequent dosing, although the trend was not significant.
3. Thus, smaller intervals between doses of hPTH-(1-34) enhance the anabolic response in bone despite the smaller doses. This effect may be secondary to 1,25-dihydroxyvitamin D3-induced increased intestinal calcium absorption, decreased 1,25-dihydroxyvitamin D3-induced bone resorption, up-regularion of osteoblast receptors for parathyroid hormone, or a combination of these three factors.