bluuebunny/crossref_metadata_2025_split huggingface dataset:
Action of Endothelin-1 on Glomerular Haemodynamics in the Dog: Lack of Direct Effects on Glomerular Ultrafiltration Coefficient
Authors: Heller Jiri , Kramer Herbert J. , Horacek Vladislav 
Published: August 2015

1. Although numerous studies have demonstrated the potent vasoconstrictor effect of endothelin-1 on the renal vasculature, it is difficult to differentiate in vivo between indirect and direct actions of endothelin.
2. In the present study we therefore performed micropuncture experiments in 14 anaesthetized dogs after the administration of endothelin-1 into the renal artery (i.r.a.) for 15 min at a dose of 2.78 ng min−1 kg−1 which did not affect blood pressure or contralateral kidney function.
3. In seven dogs on a ‘normal’ sodium diet (3.5 mmol of NaCl day−1 kg−1) endothelin-1 resulted in decreases in renal blood flow and glomerular filtration rate with a rise in filtration fraction from 0.24 ± 0.01 to 0.35 ± 0.01. Similar changes were seen at the single-nephron level. An increase from 0.11 ± 0.01 to 0.23 ± 0.02 (+ 109 ± 11%) in efferent, and from 0.15 ± 0.01 to 0.24 ± 0.02 mmHg min−1 μl−1 (+58 ± 4%) in afferent arteriolar resistance was observed. The ultrafiltration coefficient, Kf, decreased from 4.75 ± 0.14 to 3.67 ± 0.14 μl min−1 mmHg−1 (P&lt;0.01).
4. In another group of seven dogs, the same endothelin-1 infusion was given after an administration into the renal artery of a ‘cocktail’ designed to block the receptors of α- and β-adrenergic agonists, thromboxane A2, leukotrienes and angiotensin II together with intravenous cyclo-oxygenase inhibition. Under these conditions, the vasoconstrictor action of endothelin-1 was reduced by more than 30%. The increase in vascular resistance was now relatively similar in both arterioles, i.e. +44 ± 5% in the afferent and 66 ± 6% in the efferent arterioles (no significant difference). No change in Kf was seen after the ‘cocktail’-blockade (9.4 ± 0.4 versus 10.1 ± 0.1 μl min−1 mmHg−1).
5. In conclusion, in anaesthetized dogs on a ‘normal’ salt diet, the vasoconstrictor effect of endothelin-1 is more pronounced on the efferent than on the afferent arteriole. This is accompanied by decreases in glomerular filtration rate and water, urea and electrolyte excretion. Part of the vasoconstrictor action of endothelin seems to be mediated by other autacoids. Endothelin-1 itself contributes only partly to pre- and post-glomerular vasoconstriction and has no direct effect on the glomerular ultrafiltration coefficient Kf.
Central and Peripheral Haemodynamic Responses to High Carbohydrate and High Fat Meals in Human Cardiac Transplant Recipients
Authors: Kearney M. T. , Cowley A. J. , Stubbs T. A. , Perry A. J. , MacDonald I. A. 
Published: August 2015

1. Patients with autonomic dysfunction and elderly people with an age-related decline in autonomic function can suffer from a fall in blood pressure after eating. While the cardiovascular changes after eating and the effect of meal composition on these changes are well established, the underlying mechanisms are less clear.
2. This study assessed the cardiac, circulatory and humoral responses to ingestion of isoenergetic (2.5 MJ) high carbohydrate and high fat meals in nine orthotopic cardiac transplant recipients, who before transplantation had significant circulatory, metabolic and autonomic abnormalities and after transplantation had complete or partial extrinsic cardiac denervation, and compared them to the responses seen in nine healthy age-matched control subjects.
3. All variables were measured non-invasively. Cardiac transplant recipients, despite cardiac denervation, showed a normal heart rate response to high carbohydrate and high fat meals (maximal increase at 30 min postprandially +7.8 ± 1.1 and +6.3 ± 1.4 beats/min respectively), a normal cardiac output response to the high carbohydrate meal (maximal increase at 30 min +1.16 ± 0.25 l/min), but a significantly attenuated cardiac output response to the high fat meal. Cardiac transplant recipients had attenuated superior mesenteric artery blood flow responses after both meals (P &lt; 0.05) and an attenuated calf vascular resistance response after the high fat meal (P &lt; 0.01). Throughout the study after both meals, cardiac transplant recipients maintained blood pressure.
4. This study demonstrates that cardiac transplant recipients, despite partial or complete cardiac denervation, have a normal chronotropic response to food and a normal cardiac output response to a high carbohydrate meal. The attenuated cardiac output response to a high fat meal did not compromise blood pressure, due at least in part to decreased splanchnic vasodilatation.
Platelet 5-Hydroxytryptamine is Decreased in a Preliminary Group of Depressed Patients Receiving the 5-Hydroxytryptamine Re-Uptake Inhibiting Drug Fluoxetine
Authors: Menys V. C. , Smith C. C. T. , Lewins P. , Farmer R. D. T. , Noble M. I. M. 
Published: August 2015

1. In view of the importance of 5-hydroxytryptamine in coronary thrombosis, we wanted to know whether a potentially protective decrease in platelet 5-hydroxytryptamine could be achieved by treatment with an inhibitor of 5-hydroxytryptamine uptake, fluoxetine.
2. We studied 15 patients treated for psychiatric indications with fluoxetine, and compared the findings with those obtained with blood from 18 patients treated with amitriptyline and 13 controls previously treated for affective disorders.
3. Platelet-rich plasma 5-hydroxytryptamine levels were significantly decreased in the fluoxetine group (P &gt; 0.005) but not in the amitriptyline group compared with the control group.
4. Collagen-induced aggregation in whole blood anti-coagulated with hirudin was measured by sequential single platelet counting. The contribution of 5-hydroxytryptamine was assessed from the effect of adding the 5-hydroxytryptamine specific antagonist ICI 170809. This contribution was significantly decreased in the fluoxetine group but not in the amitriptyline group compared with the control group.
5. It is concluded that platelet 5-hydroxytryptamine is indeed decreased by fluoxetine, and we would predict a protective effect of fluoxetine against coronary thrombosis.
Effects of Adrenaline Infusion on the Interstitial Environment of Subcutaneous Adipose Tissue as Studied by Microdialysis
Authors: Samra J. S. , Simpson E. J. , Clark M. L. , Forster C. D. , Humphreys S. M. , MacDonald I. A. , Frayn K. N. 
Published: August 2015

1. Adrenaline was infused at a rate of 25 ng min−1 kg−1 into seven healthy volunteers and its effects on adipose tissue were studied by microdialysis.
2. Adrenaline infusion led to a rapid rise in plasma adrenaline concentration from a basal value of 0.15 ± 0.03 nmol/l to a peak value of 1.82 ± 0.15 nmol/l within 30 min (analysis of variance: P &lt; 0.001). Plasma noradrenaline levels increased from the basal value of 1.48 ± 0.21 nmol/l to 1.78 ± 0.20 nmol/l within 30 min of infusion (analysis of variance: P &lt; 0.05). Once the infusion was stopped the plasma adrenaline and noradrenaline levels returned to basal values within 15 min.
3. The arterialized blood glycerol concentration increased from the basal value of 47 ± 6μmol/l to 101 ± 8 μmol/l (analysis of variance: P &lt; 0.001), and the interstitial glycerol concentration increased from 181 ± 17 μmol/l to 350 ± 47μmol/l (analysis of variance: P &lt; 0.001) within 30 min of adrenaline infusion. Thereafter the concentrations declined gradually towards basal values. When the infusion was discontinued the levels declined further, below the basal value.
4. Adrenaline infusion caused a significant increase in the plasma glucose and blood lactate concentration (analysis of variance: P &lt; 0.001 and P &lt; 0.001), but no such effect was observed in the interstitial concentrations.
5. The basal dialysate concentrations of adrenaline and noradrenaline were 43 ± 37 pmol/l and 1170 ± 430 pmol/l respectively. There were difficulties in estimating the absolute interstitial concentrations of adrenaline and noradrenaline which are discussed. The dialysate adrenaline concentration increased to a peak value of 112 ± 48 pmol/l (analysis of variance: P &lt; 0.05) within 30 min. The dialysate noradrenaline concentration increased to a peak value of 2830 ± 1470 pmol/l, but the rise was not significant.
6. These results show that the interstitial concentrations of metabolites and hormones can be significantly different from those of blood and plasma and these differences reflect tissue specialization.
Blood Transfusion Enhances Production of T-Helper-2 Cytokines and Transforming Growth Factor β in Humans
Authors: Gafter Uzi , Kalechman Yona , Sredni Benjamin 
Published: August 2015

1. Blood transfusion confers immune suppression with improved allograft survival. The aim of this study was to evaluate the effect of blood transfusion on the production of T-helper-2 cytokines and transforming growth factor β, which are associated with suppression of allograft rejection. An additional aim was to try to identify which blood cell type is mostly responsible for the blood transfusion effect. Production of interleukin-4, interleukin-10 and transforming growth factor β by peripheral blood mononuclear cells isolated from patients with end-stage renal disease was measured in vitro. These assays were performed before, and 4 h, 4, 7 and 14 days after a single blood transfusion and the transfusion of one unit of leucocyte-free erythrocytes.
2. Blood transfusion stimulated a significant rise in the production of all three cytokines measured. Transfusion of erythrocytes had no effect on the production of interleukin-4 or interleukin-10.
3. It is suggested that blood transfusion enhances the production of interleukin-4, interleukin-10 and transforming growth factor β. These cytokines may inhibit production of T-helper 1 and pro-inflammatory cytokines, deactivate cytotoxic cells and thereby suppress allograft rejection. It is further suggested that the leucocyte is the transfused cell type which is mostly associated with induction of this immunosuppressive response.
Weanling Rats Exposed to Maternal Low-Protein Diets during Discrete Periods of Gestation Exhibit Differing Severity of Hypertension
Authors: Langley-Evans Simon C. , Welham Simon J. M. , Sherman Rachel C. , Jackson Alan A. 
Published: August 2015

1. In the rat, hypertension is induced by fetal exposure to maternal low-protein diets. The effect on blood pressure of undernutrition before conception and during discrete periods in early, mid or late pregnancy was assessed using an 18% casein (control) diet and a 9% casein diet to apply mild protein restriction.
2. The offspring of rats fed 9% casein developed raised blood pressure by weaning age. Feeding a low-protein diet before conception was not a prerequisite for programming of hypertension.
3. Hypertension was observed in rats exposed to low protein during the following gestational periods: days 0–7, days 8–14 and days 15–22. Blood pressure increases elicited by these discrete periods of undernutrition were lower than those induced by feeding a low-protein diet throughout pregnancy. The effect in early gestation was significant only in male animals. Post-natal growth of male rats exposed to low-protein diets was accelerated, but kidneys were small in relation to body weight.
4. Biochemical indices of glucocorticoid action in liver, hippocampus, hypothalamus and lung were elevated in rats exposed to low-protein diets in utero. The apparent hypersensitivity to glucocorticoids was primarily associated with undernutrition in mid to late gestation.
5. Plasma renin activity was elevated in rats exposed to 9% casein over days 15–22 of gestation. Animals undernourished over days 0–7 and 8–14 produced pups with lower plasma angiotensin II concentrations at weaning.
6. Fetal exposure to maternal low-protein diets for any period in gestation may programme hypertension in the rat. Alterations to renal structure, renal hormone action or the hypothalamic—pituitary-adrenal axis may all play a role in the programming phenomenon, either independently or in concert.
α-Adrenoceptor Mechanisms of Thermoregulation during Cold Challenge in Humans
Authors: Frank Steven M. , El-Gamal Nader , Raja Srinivasa N. , Wu Peter K. 
Published: August 2015

1. Previous studies on the thermoregulatory effects of α-adrenoceptor antagonists have been performed primarily in animals and the findings have been inconsistent. There is evidence for thermoregulatory impairment by α-adrenergic antagonists in humans not exposed to cold, but the effects of α-adrenergic blockade during cold challenge have not been investigated.
2. Fourteen healthy human volunteers (seven elderly, aged 55–68 years and seven young, aged 19–27 years) were studied on three separate days and received three randomly assigned treatments: (i) control (no drug), (ii) low-dose phentolamine, and (iii) high-dose phentolamine. On each day cold intravenous saline (4°C) was given until both vasoconstriction and shivering were triggered or a maximum fluid volume (40 ml/kg) was delivered. Core temperature, peripheral vasoconstriction and metabolic heat production were measured.
3. The α-adrenoceptor antagonist caused a dose-dependent inhibition of vasoconstriction in the elderly but did not impair vasoconstriction in the young subjects at the doses that were given. Shivering and metabolic heat production were unaffected by α-adrenergic blockade in the elderly or in the young.
4. These findings illustrate the selective inhibition of vasoconstriction (but not shivering) by α-adrenoceptor antagonism in elderly individuals. Compared with the young, the elderly are more sensitive to the effects of α-antagonists, perhaps due to downregulation of the α-adrenoceptor. These findings lead us to conclude that thermoregulatory vasoconstriction is α-adrenergically mediated, and this response is attenuated by α-adrenoceptor blockade in elderly humans.
Na+,K+-ATPase of Human Placenta during Gestational Hypertension: A Biochemical—Biophysical Study
Authors: Rabini Rosa A. , Zolese Giovanna , Staffolani Roberto , Lucarelli G. , Amler E. , Cester Nelvio , Mazzanti Laura 
Published: August 2015

1. Na+,K+-ATPase is the membrane enzyme catalysing the active transport of Na+ and K+ across the plasma membrane of animal cells. A reduced activity of Na+,K+-ATPase has been described in gestational hypertension in a variety of cell types, in agreement with the hypothesis that gestational hypertension can induce membrane transport modifications similar to those reported for essential hypertension. The causes of the reduced Na+,K+-ATPase activity are still debated.
2. The aim of the present work was to investigate the molecular mechanism of the reduced enzymic activity in gestational hypertension using as a model Na+,K+-ATPase purified from human placenta. Na+,K+-ATPase obtained from term placentas of eight healthy pregnant women and eight age-matched women with gestational hypertension was purified as previously described.
3. We observed in gestational hypertension: (i) a significant increase in the activation energies above transition temperature; (ii) a significant decrease in the fluorescence polarization of 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (i.e. increased fluidity) and an increase in the mean lifetime (modified hydrophobicity); (iii) a lower Kq, suggesting an enzymic structural modification; and (iv) an increased mean lifetime and rotational relaxation time of pyrene isothiocyanate, indicating a modified ATP binding site.
Understanding the Molecular Basis of Cell Migration; Implications for Clinical Therapy in Multiple Sclerosis
Authors: Milner Richard 
Published: August 2015

1. Multiple sclerosis is characterized by areas of demyelination spread throughout the central nervous system, in which the myelin sheaths surrounding axons are destroyed. While therapies aimed at suppressing the autoimmune response, such as β-interferon, may prevent further damage, they cannot repair or replace the lost myelin. To this end, an additional therapy has been proposed, which involves transplanting cells of the oligodendrocyte lineage into the central nervous system.
2. The cell of interest for transplantation is the oligodendrocyte precursor because, unlike the differentiated cell, it is an intrinsically migratory and proliferative cell. In order to optimize the transplant strategy we have investigated the molecular mechanisms that control migration in vitro, so that these mechanisms might be upregulated to maximize cell migration in vivo. We have focused on the integrin family of cell adhesion molecules, known to play a fundamental role in the regulation of migration in other cell types.
3. These studies show that oligodendrocytes express a limited repertoire of integrins consisting of α6β1 and three different αv integrins. α6β1 is expressed throughout development but αv integrins show developmental regulation; differentiation is accompanied by loss of αvβ1 and upregulation of αvβ5.
4. Function-blocking studies show that oligodendrocyte precursor migration in vitro is mediated primarily by the developmentally regulated αvβ1 integrin, but not α6β1 or αvβ3. Taken together with previous evidence that cell migration can be regulated by altering integrin expression, this work suggests that modifying expression levels of αvβ1 on oligodendrocyte precursors may increase the migratory capacity of these cells. If so, this would support a future therapeutic strategy aimed at transplanting genetically modified oligodendrocyte precursors to repair widespread demyelinated lesions.
Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels
Authors: Shiramoto Masanari , Imaizumi Tsutomu , Hirooka Yoshitaka , Endo Toyonari , Namba Takashi , Oyama Jun-Ichi , Hironaga Kiyoshi , Takeshita Akira 
Published: August 2015

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans.
2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg).
3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation.
4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.
Gene Therapy for Diabetes Mellitus
Authors: Docherty Kevin 
Published: August 2015

1. This review describes experimental approaches to test the feasibility of using gene therapy to administer insulin to type 1 and type 2 diabetic patients. Two approaches, i.e. ex vivo and in vivo transfer of the insulin gene, are described.
2. Substantial progress has been made in recent years in engineering glucose-responsive β-cell lines that have been genetically engineered to proliferate or differentiate in response to appropriate extracellular signals.
3. Non-β-cell lines have been engineered to constitutively secrete insulin at a constant rate. These cells may improve glycaemic control in patients over longer periods when used in combination with insulin injections. Engineering glucose-stimulated insulin secretion in such cells has proved extremely difficult and several genes may be required.
4. In vivo transfer of the insulin gene to animals results in improved control of diabetes. However, for safety reasons this approach may have limited use in the treatment of diabetes in humans.
Fractal Component of Variability of Heart Rate and Systolic Blood Pressure in Congestive Heart Failure
Authors: Butler Gary C. , Ando Shin-Ichi , Floras John S. 
Published: August 2015

1. There is a substantial non-harmonic or fractal component to the variability of both heart rate and blood pressure in normal subjects. Heart rate is the more complex of these two signals, with respect to the slope, β, of the 1/fβ relationship. In congestive heart failure, heart rate spectral power is attenuated, but the fractal and harmonic components of heart rate and systolic blood pressure variability have not been characterized.
2. Two groups, each comprising 20 men, were studied during 15 min of supine rest and spontaneous respiration: one with functional class II—IV heart failure (age 52 ± 2 years; mean ± SEM) and a second group of healthy men (age 46 ± 2 years).
3. Total spectral power for heart rate was significantly reduced in heart failure (P &lt; 0.02), whereas total spectral power for systolic blood pressure was similar in the two groups. In both heart failure and normal subjects, 65–80% of total spectral power in these two signals displayed fractal characteristics.
4. In heart failure, the slope of the 1/fβ relationship for heart rate was significantly steeper than in normal subjects (1.40 ± 0.08 compared with 1.14 ± 0.05; P &lt; 0.05), indicating reduced complexity of the fractal component of heart rate variability. There was no significant difference in the 1/fβ slope for systolic blood pressure variability between these two groups, but the blood pressure signals were less complex than heart rate variations in both heart failure (2.31 ± 0.15; P &lt; 0.006) and normal subjects (2.47 ± 0.15; P &lt; 0.0001).
5. Parasympathetic nervous system activity, as estimated from heart rate variability was reduced (P &lt; 0.01) in patients with heart failure, whereas trends towards increased sympathetic nervous system activity and decreased non-harmonic power were not significant.
6. The non-harmonic components of cardiac frequency are reduced in heart failure. Non-harmonic power is not attenuated, but the complexity of the heart rate signal is less than in subjects with normal ventricular function. A reduction in parasympathetic modulation appears to contribute to this loss of complexity of heart rate. Consequently, the heart rate signal comes to resemble that of blood pressure. In contrast, the variability and complexity of the systolic blood pressure signal is similar in heart failure and normal subjects. This reduced complexity of heart rate variability may have adverse implications for patients with heart failure.