bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Effects of Acute Hyperketonaemia in Man before and during An Hyperinsulinaemic Euglycaemic Clamp
Authors: Webber J. , Simpson E. , Parkin H. , MacDonald I. A. 
Published: August 2015

1. The effects of acutely raising blood ketone body levels to those seen after 72 h of starvation were examined in 10 subjects after an overnight fast. Metabolic rate and respiratory exchange ratio were measured with indirect calorimetry before and during an insulin—glucose clamp. Arteriovenous differences were measured across forearm and subcutaneous abdominal adipose tissue.
2. In response to the clamp the respiratory exchange ratio rose from 0.82 to 0.83 during 3-hydroxybutyrate infusion and from 0.83 to 0.94 during control (saline) infusion (P &lt; 0.001).
3. Forearm glucose uptake at the end of the clamp was 4.02 ± 0.95 (3-hydroxybutyrate infusion) and 7.09 ± 1.24 mmol min−1 100 ml−1 forearm (saline infusion). Whole body glucose uptake at the end of the clamp was 72.8 ± 7.9 (3-hydroxybutyrate infusion) and 51.0 ± 3.0 (saline infusion) mmol min−1 kg−1 body weight−1.
4. 3-Hydroxybutyrate infusion reduced the baseline abdominal venous—arterialized venous glycerol difference from 84 ± 28 to 25 ± 12 mmol/l and the non-esterified fatty acid difference from 0.60 ± 0.17 to 0.02 ± 0.09 mmol/l (P &lt; 0.05 versus saline infusion).
5. Hyperketonaemia reduces adipose tissue lipolysis and decreases insulin-mediated forearm glucose uptake. Hyperketonaemia appears to prevent insulin-stimulated glucose oxidation, but does not reduce insulin-mediated glucose storage.
Oxygen Reactivity in Diabetes Mellitus: Effect of Hypertension and Hyperglycaemia
Authors: Patel V. , Rassam S. M. B. , Chen H. C. , Kohner E. M. 
Published: August 2015

1. Laser Doppler velocimetry and computerized image analysis of retinal photographs were used to define retinal vascular autoregulation to 60% oxygen breathing. This normally causes vasoconstriction in the retinal circulation. Normotensive and hypertensive diabetic subjects were studied under conditions of relative normoglycaemia (&lt; 10 mmol) and hyperglycaemia (&gt; 15 mmol) together with control subjects.
2. Retinal blood flow was significantly higher in diabetic subjects when hypertensive and hyperglycaemic than in the same diabetic subjects when normotensive.
3. In the normotensive non-diabetic subjects the oxygen reactivity was 41.16 ± 14.09%. It was significantly reduced in normotensive ‘hyperglycaemic’ diabetic subjects (21.75 ± 15.56%), hypertensive diabetic subjects with controlled blood pressure and ‘normoglycaemia’ (30.49 ±14.20%), hypertensive diabetic subjects with controlled blood pressure and ‘hyperglycaemia’ (18.36 ±11.42%), hypertensive diabetic subjects with uncontrolled blood pressure and ‘normoglycaemia’ (26.91 ±13.43%) and hypertensive diabetic subjects with uncontrolled blood pressure and ‘hyperglycaemia’ (17.17 ±13.24%) (means±SD, all P values &lt;0.05).
4. In conclusion, retinal vascular reactivity is impaired in diabetic subjects both when they are normotensive and when they are hypertensive. Hyperglycaemia, to a degree commonly encountered in clinical practice, impairs retinal vascular autoregulation even further.
Flow Cytometric Detection of Circulating Activated Platelets and Platelet Hyper-Responsiveness in Pre-Eclampsia and Pregnancy
Authors: Janes Sarah L. , Goodall Alison H. 
Published: August 2015

1. Platelet activation status and response to stimulation with agonists ex vivo were studied by whole blood flow cytometry in 15 women with pre-eclampsia, 20 age- and gestational-age-matched women who completed a normal pregnancy, and 20 age-matched non-pregnant women.
2. Women with proteinuric pre-eclampsia showed evidence of activated, degranulated platelets in the circulation, with increased platelet-bound fibrinogen, increased expression of the lysosomal granule membrane antigen, CD63, and raised plasma levels of β-thromboglobulin.
3. CD63 expression and β-thromboglobulin per platelet were also significantly higher in normal pregnant women than in non-pregnant women, but in these subjects fibrinogen binding was normal.
4. There was good correlation for all subjects in degranulation, measured by CD63 antigen expression, and by plasma β-thromboglobulin levels corrected for platelet count (r = 0.65; P &lt; 0.01).
5. Platelet responsiveness to ADP in vitro showed a heightened degranulation response (CD63 expression) in normal pregnancy compared with the non-pregnant control group, which was increased further in women with non-proteinuric and proteinuric pre-eclampsia.
6. However, this response was not accompanied by an increased binding of fibrinogen to GPIIb—IIIa. Fibrinogen binding in response to ‘weak’ agonist stimulation, by low concentrations of ADP or, in a subgroup by adrenaline, was in fact lower in the normal pregnant women than in the non-pregnant women.
7. It is postulated that women at risk of developing pre-eclampsia may have hyper-reactive platelets, primed to undergo release by passage through the abnormal placenta.
Epidemiology of An Outbreak of Drug-Resistant Tuberculosis in the U.K. Using Restriction Fragment Length Polymorphism
Authors: Goyal M. , Ormerod L. P. , Shaw R. J. 
Published: August 2015

1. Drug-resistant tuberculosis is a growing health care problem. When a series of cases occur, it is essential to know if patients with multidrug-resistant disease represent one or a number of separate outbreaks.
2. The epidemiology of an outbreak of isoniazid- and streptomycin-resistant tuberculosis in Blackburn was studied by restriction fragment length polymorphism using a probe for the IS6110 DNA sequence.
3. Mycobacterium tuberculosis from four cases of isoniazid- and streptomycin-resistant disease had an identical restriction fragment length polymorphism pattern. This pattern was not shared by drug-sensitive isolates of M. tuberculosis obtained from Blackburn (n = 8) or London (n = 13) or a M. tuberculosis isolate from a fifth Blackburn case which was resistant to isoniazid alone.
4. This methodology confirmed that all four cases of isoniazid- and streptomycin-resistant disease were part of a single epidemiologically related outbreak of drug-resistant disease. This study demonstrates how the epidemiology of an outbreak of multidrug-resistant tuberculosis in the U.K. can be confirmed by restriction fragment length polymorphism.
l-Arginine Reverses the Impairment of Nitric Oxide-Dependent Collateral Perfusion in Dietary-Induced Hypercholesterolaemia in the Rabbit
Authors: Randall Michael D. , Ujiie Hiroshi , Griffith Tudor M. 
Published: August 2015

1. We have used an isolated, buffer-perfused, rabbit ear model of acute arterial occlusion to investigate the effects of exogenous l-arginine on the severe impairment of collateral perfusion associated with dietary-induced hypercholesterolaemia. The effects of l-arginine on hypercholesterolaemia-related impairment of endothelium-dependent relaxations to acetylcholine were also investigated in unligated, isolated rabbit ears perfused with buffer.
2. Cholesterol feeding for 8 weeks (blood cholesterol level 66.5 ± 5.3 versus 1.4 ± 0.2 mmol/l, P &lt; 0.001) was associated with almost complete impairment of collateral perfusion, an effect previously observed after inhibition of nitric oxide synthesis. The impairment of collateral perfusion found in hypercholesterolaemia was completely reversed by the addition of 10 mmol/l l-arginine to the perfusion fluid. In control preparations from rabbits fed a normal diet, the addition of 10 mmol/l l-arginine did not influence collateral perfusion.
3. Endothelium-dependent relaxation to acetylcholine was impaired in preparations from the rabbits fed the high cholesterol diet for 8 weeks: the maximum relaxation of tone was 24.6 ± 0.8% and was significantly (P &lt; 0.01) less than that in the controls (70.3 ± 2.4%). Addition of l-arginine to the perfusion fluid caused a modest improvement in the endothelium-dependent relaxations to acetylcholine, with a maximum response of 43.2 ± 1.3%.
4. We conclude that nitric oxide-dependent collateral perfusion is severely impaired in hypercholesterolaemia and that the addition of exogenous l-arginine fully reverses these changes. Endothelium-dependent relaxations to acetylcholine are similarly impaired by hypercholesterolaemia; however, this deficit was only partially reversed by l-arginine. In the context of collateral perfusion, l-arginine treatment may represent a therapeutic strategy to limit the deleterious effects of hypercholesterolaemia on acute arterial occlusion.
Complex Modulation of Cytokine Induction by Endotoxin and Tumour Necrosis Factor from Peritoneal Macrophages of Rats by Diets Containing Fats of Different Saturated, Monounsaturated and Polyunsaturated Fatty Acid Composition
Authors: Tappia P. S. , Grimble R. F. 
Published: August 2015

1. Responses to cytokines and other inflammatory stimuli have been shown to be enhanced by fats rich in n − 6 polyunsaturated fatty acids and suppressed by fats rich in n − 3 polyunsaturated fatty acids and oleic acid or poor in n − 6 polyunsaturated fatty acids.
2. Corn oil is rich and coconut oil, olive oil and butter are poor in n − 6 polyunsaturated fatty acids. Olive oil and butter are rich in oleic acid. Fish oil is rich in n − 3 polyunsaturated fatty acids.
3. The present study examines the effects of feeding standard chow or corn, coconut, fish and olive oils and butter for 4 and 8 weeks on subsequent cytokine production by peritoneal macrophages of rats.
4. Tumour necrosis factor production in response to a lipopolysaccharide stimulus and interleukin-1 and interleukin-6 production in response to a tumour necrosis factor challenge were studied.
5. All fats produced a small, but statistically insignificant, reduction in tumour necrosis factor production, which was greatest for olive oil at 8 weeks.
6. After 4 weeks, fish and olive oil significantly reduced interleukin-1 production. After 8 weeks, coconut oil suppressed production of the cytokine, and the inhibitory effect of fish oil was still apparent. After 8 weeks, corn and olive oil enhanced interleukin-1 production.
7. After 4 weeks of feeding, fish and olive oil enhanced interleukin-6 production. After 8 weeks, the enhancement by these fats increased, and corn oil and butter also enhanced production. Coconut oil produced no modulatory effect.
8. Only in the cases of the effect of fish and coconut oil in interleukin-1 production, corn oil on interleukin-1 and interleukin-6 production and olive oil in tumour necrosis factor production, were the effects of fats on cytokine production in concordance with their modulatory effects on responses to cytokines and other inflammatory agents in vivo.
Acute Alcohol Intake Decreases Short-Term Heart Rate Variability in Healthy Subjects
Authors: Koskinen Pekka , Virolainen Juha , Kupari Markku 
Published: August 2015

1. The acute effects of a moderate dose of ethanol (1 g/kg body weight) on heart rate and blood pressure variability and baroreflex sensitivity were studied in 12 healthy male subjects in a juice-controlled experiment. Electrocardiographic and finger blood pressure data were recorded and stored in a minicomputer during 5 min of controlled breathing (15 cycles/min) and during deep breathing (5 s inpiration, 5 s expiration, four cycles) before drinking and hourly thereafter for 3 h.
2. Mean breath alcohol concentration rose to 18.9 mg/100 ml. In the time domain analysis, the root mean square difference of successive R-R interval decreased significantly with ethanol as compared with the juice experiment. The difference remained statistically significant even after adjustment for the shorter R-R interval after alcohol. In the frequency domain analysis the high-frequency (0.15-0.5 Hz) spectral power showed a significant decrease after alcohol intake. Also, the index of sensitivity of the baro-receptor reflex (square root of R-R interval power/systolic blood pressure power) decreased significantly in the high-frequency component. Ethanol did not change finger systolic blood pressure, and power spectral analysis did not show significant variability in blood pressure.
3. These data indicate that acute intake of moderate amounts of alcohol causes a significant decrease in heart rate variability owing to diminished vagal modulation of the heart rate.
Effect of ‘Autonomic Blockade’ on Cardiac β-Adrenergic Chronotropic Responsiveness in Healthy Young, Healthy Elderly and Endurance-Trained Elderly Subjects
Authors: Ford G. A. , James O. F. W. 
Published: August 2015

1. Cardiac chronotropic responses to isoprenaline are reduced with ageing in man. It is unclear whether this is due to reduced cardiac β-adrenergic sensitivity or to age-associated differences in reflex cardiovascular responses to the vasodilatory effects of isoprenaline. Age-associated changes in physical activity are also reported to influence β-adrenergic sensitivity.
2. The aim of the present study was to determine the contribution of alterations in reflex changes in parasympathetic and sympathetic influences and physical fitness to the age-associated reduction in cardiac chronotropic responses to β-adrenergic agonists.
3. The effect of ‘autonomic blockade’ with atropine (40 μg/kg intravenously) and clonidine (4 μg/kg intravenously) on blood pressure, heart rate and chronotropic responses to intravenous bolus isoprenaline doses was determined in eight healthy young (mean age 21 years), nine healthy elderly (72 years) and 10 endurance-trained elderly (69 years) subjects.
4. Elderly subjects had a reduced increase in heart rate after atropine (young, 49 ± 9 beats/min; elderly, 36 ± 5 beats/min; endurance-trained elderly, 34 ± 12 beats/min; P &lt; 0.01) and did not demonstrate the transient increase in systolic blood pressure after clonidine observed in young subjects (young, 11 ± 10 mmHg; elderly, −12 ± 16 mmHg; endurance-trained elderly, −18 ± 11 mmHg; P &lt; 0.01).
5. Cardiac chronotropic sensitivity to isoprenaline after ‘autonomic blockade’ increased in the young but decreased in the elderly subjects. The isoprenaline dose that increased heart rate by 25 beats/min before and after autonomic blockade' was: young, before 1.6 μg, after 2.8 μg, P &lt; 0.01 (geometric mean, paired test); elderly, before 6.9 μg, after 3.6 μg, P &lt; 0.05; endurance-trained elderly, before 5.9 μg, after 4.0 μg, P &lt; 0.05. Cardiac chronotropic sensitivity to isoprenaline was significantly reduced in elderly compared with young subjects before (P &lt; 0.01) but was similar after (P = 0.09) ‘autonomic blockade’. Chronotropic sensitivity did not differ between healthy and endurance-trained elderly subjects before or after ‘autonomic blockade’.
6. The age-associated reduction in cardiac chronotropic responses to bolus isoprenaline is primarily due to an age-related reduction in the influence of reflex cardiovascular responses on heart rate and not to an age-related reduction in cardiac β-adrenergic sensitivity. Endurance training is not associated with altered β-adrenergic chronotropic sensitivity in the elderly. The transient pressor response to intravenously administered clonidine may be lost in ageing man.
Elevated Plasma C-Type Natriuretic Peptide Concentrations in Patients with Chronic Renal Failure
Authors: Totsune Kazuhito , Takahashi Kazuhiro , Murakami Osamu , Satoh Fumitoshi , Sone Masahiko , Mouri Toraichi 
Published: August 2015

1. C-type natriuretic peptide is a neuropeptide, which is also produced by the vascular endothelial cells. Plasma immunoreactive C-type natriuretic peptide concentrations in patients with various diseases have not yet been studied.
2. Plasma immunoreactive C-type natriuretic peptide concentrations were studied by radioimmunoassay in normal subjects, patients with congestive heart failure, non-dialysed patients with chronic renal failure and haemodialysis patients with chronic renal failure. The C-type natriuretic peptide levels were compared with the levels of atrial natriuretic peptide and brain natriuretic peptide.
3. Plasma immunoreactive C-type natriuretic peptide concentrations were greatly elevated in patients with chronic renal failure [non-dialysed, 13.0 ± 4.2 pmol/l (mean ± SEM), n = 9, P &lt; 0.01) compared with normal subjects (4.4 ± 0.4 pmol/l, n = 26); haemodialysis, 16.1 ± 2.1 pmol/l, n = 13, P &lt; 0.01], but not in patients with congestive heart failure (New York Heart Association Class II-IV, 3.0 ± 0.7 pmol/l, n = 11, P &gt; 0.05). Plasma immunoreactive atrial natriuretic peptide and brain natriuretic peptide concentrations were elevated both in patients with congestive heart failure and in haemodialysis patients with chronic renal failure.
4. Reverse-phase high performance liquid chromatography showed that immunoreactive C-type natriuretic peptide in plasma from normal subjects and haemodialysis patients was eluted in the positions of C-type natriuretic peptide −22 and −53.
5. These findings suggest that C-type natriuretic peptide is a non-cardiac circulating hormone and participates in the cardiovascular regulation in a different manner from atrial natriuretic peptide and brain natriuretic peptide.
Atrial Natriuretic Peptide Inhibits Cyclosporin A-Induced Endothelin Production and Calcium Accumulation in Rat Vascular Smooth Muscle Cells
Authors: Bokemeyer Dirk , Friedrichs Ursula , Bäcker Angela , Drechsler Sabine , Kramer Herbert J. , Meyer-Lehnert Harald 
Published: August 2015

1. As we have previously shown, cyclosporin A enhances the vasoconstrictor-induced rise in intracellular free calcium in vascular smooth muscle cells. This effect may contribute to important side-effects in cyclosporin therapy, such as hypertension and nephrotoxicity. Atrial natriuretic peptide has been shown to inhibit this effect as well as the cyclosporin-stimulated transmembrane calcium influx in smooth muscle cells.
2. The present study, therefore, was designed to examine the effect of cyclosporin and atrial natriuretic peptide on total cellular calcium content in the rat. Furthermore, since cyclosporin was recently shown to induce endothelin production in smooth muscle cells, we investigated the effect of atrial natriuretic peptide on this potentially adverse cellular effect of cyclosporin therapy.
3. Total cell calcium was measured by atomic absorption, and cellular endothelin production was estimated by radioimmunoassay.
4. Preincubation of the cells with cyclosporin (10 μg/ml) for 30 min increased total cell calcium from 2.6 ± 0.5 to 6.9 ± 0.3 nmol/mg of protein (P &lt; 0.01). Within 24 h endothelin production was significantly enhanced in the presence of cyclosporin (52.2 ± 2.5 versus 65.9 ± 2.7 fmol/mg of protein, P &lt; 0.05). Therefore, the cyclosporin-induced rise in total cell calcium in smooth muscle cells is associated with enhanced production of enthothelin. Thus, it is tempting to speculate that the cyclosporin-induced changes in calcium kinetics may be mediated by endothelin.
5. In the presence of atrial natriuretic peptide (10-8 mol/l), the cyclosporin-induced rise in total cell calcium was significantly reduced (6.9 ± 0.3 versus 5.1 ± 0.2 nmol/mg of protein, P &lt; 0.05). In the presence of atrial natriuretic peptide (5 × 10−9 mol/l) cyclosporin A did not affect the production of endothelin in smooth muscle cells (453 ± 3.5 versus 50.1 ± 2.8 fmol/mg of protein, not significant).
6. These results indicate that endothelin may play a major role in cyclosporin-associated side-effects. By inhibiting the cyclosporin-stimulated production of endothelin, atrial natriuretic peptide may have a beneficial effect on cyclosporin-associated hypertension and nephrotoxicity.
Primary Localized Orbital Amyloidosis Composed of the Immunoglobulin γ Heavy Chain CH3 Domain
Authors: Tan S. Y. , Murdoch I. E. , Sullivan T. J. , Wright J. E. , Truong Oanh , Hsuan J. J. , Hawkins P. N. , Pepys M. B. 
Published: August 2015

1. Primary orbital amyloidosis is a rare form of localized amyloidosis in which the precursor protein has not previously been identified. We report here the first extraction of amyloid fibrils from a tissue biopsy containing orbital amyloid, and characterization of the fibril protein.
2. The N-terminal nine residues were identical with residues 278–286 and 275–283 of the third constant (CH3) domains of IgG1 and IgG4 γ heavy chains, respectively. The mass of the fibril subunit protein was 6125 Da by time-of-flight mass spectrometry, compared with the expected masses of 6169.9 Da and 6214.9 Da for the CH3 domains of γ1 from residue 278 and γ4 from residue 275, respectively. The fibril protein thus appeared to consist exclusively of an immunoglobulin heavy chain constant domain.
3. Only two examples of immunoglobulin heavy chain derived amyloid have been reported previously and both of these, as well as all published cases of the usual immunoglobulin light chain derived amyloid, contained variable domain sequence. The present case therefore represents a form of local, presumably clonal, B-cell/plasma-cell disorder characterized uniquely by deposition of an amyloidogenic immunoglobulin heavy chain constant domain fragment.
Serum Vitamin A and E Concentrations in Acute Falciparum Malaria: Modulators or Markers of Severity?
Authors: Davis Timothy M. E. , Binh Tran Quang , Danh Phan Thi , Dyer John R. , St John Andrew , Garcia-Webb Peter , Anh Trinh Kim 
Published: August 2015

1. To assess the association between vitamin A, vitamin E and the clinical course of severe malaria, serial morning blood samples were taken from 24 Vietnamese patients, aged 18–62 years, receiving intensive treatment for complicated Plasmodium falciparum infections. A single fasting blood sample was also taken from 10 control subjects aged 22–45 years. Serum retinol, carotene and vitamin E concentrations were measured by h.p.l.c.
2. Admission serum retinol concentration was depressed relative to that of the control subjects (0.69 ± 0.35 versus 1.86 ± 0.41μmol/l mean ± SD, P &lt; 0.001) and correlated inversely with indices of hepatic function, but positively with the simultaneous serum creatinine concentration (P &lt; 0.05). During the first week of treatment, serum retinol concentration increased in parallel with improving liver function, whereas serum creatinine concentration remained elevated in the majority of patients. Serum α- and β-carotene concentrations remained depressed throughout.
3. Serum vitamin E concentration, corrected for total serum cholesterol concentration in the form of a ratio, was also depressed at presentation (3.1 ± 1.8×103 versus 4.2 ± 0.8×103 in control subjects; P &lt; 0.05), but tended to be higher than the control value at the time of discharge (0.1 &gt; P &gt; 0.05); there was a significant correlation between admission ratio and parasite clearance time (P = 0.04).
4. On the basis of this and previous studies, vitamin A replacement could be considered in selected severely ill patients without renal impairment. As found previously in animal models, depressed vitamin E levels may have a beneficial effect on the course of malarial infection.