bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ischaemia—Reperfusion Injury in the Rat is Modulated by Superoxide Generation and Leads to An Augmentation of the Hypoxic Pulmonary Vascular Response
Authors: Messent Mark , Griffiths Mark J. D. , Quinlan Gregory J. , Gutteridge John M. C. , Evans Timothy W. 
Published: August 2015

1. The effects of the scavengers of reactive oxygen species superoxide dismutase and catalase, the iron chelator desferrioxamine and the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester and saline (control vehicle) on hypoxic pulmonary vasoconstriction, a measure of albumin flux and an index of lipid peroxidation (palmitic:linoleic acid ratio) were investigated after ischaemia—reperfusion in an isolated, blood-perfused rat lung model.
2. Lungs treated immediately before reperfusion with catalase (5 000 units), desferrioxamine (2 mg/kg), NG-nitro-l-arginine methyl ester (5 mmol/l) or saline showed a significant augmentation in pre-ischaemia—reperfusion hypoxic pulmonary vasoconstriction (57.7 ± 6.0%, 82.7 ± 28.8%, 95.2 ± 36.6% and 45.95 ± 10.53% respectively), an increase in albumin flux (0.35 ± 0.04, 0.31 ± 0.06, 0.29 ± 0.04 and 0.33 ± 0.02) and an increase in pre-ischaemia—reperfusion palmitic:linoleic acid ratio (0.64 ± 0.08, 0.51 ± 0.19, 0.5 ± 0.04 and 0.17 ± 0.07). Superoxide dismutase (2 750 i.u.) administered immediately before reperfusion prevented completely the changes in hypoxic pulmonary vasoconstriction (−0.3 ± 5.4%), albumin flux (0.09 ± 0.11) and palmitic:linoleic acid ratio (–0.06 ± 0.12). In control lungs (2 h of continuous perfusion), superoxide dismutase, catalase, desferrioxamine and saline did not affect hypoxic pulmonary vasoconstriction (5.5 ± 4.9%, 1.0 ± 3.1%, −5.1 ± 1.8% and 3.0 ± 6.6%). However, NG-nitro-l-arginine methyl ester significantly augmented hypoxic pulmonary vasoconstriction (275.1 ± 39.3%). There was no effect of superoxide dismutase, catalase, desferrioxamine, NG-nitro-l-arginine methyl ester or saline in control lungs on albumin flux (0.10 ± 0.04, 0.11 ± 0.01, 0.1 ± 0.01, 0.12 ± 0.01 and 0.11 ± 0.01 respectively) or palmitic:linoleic acid ratio (–0.08 ± 0.08, 0.73 ± 0.76, −0.03 ± 0.12, 0.01 ± 0.17 and 0.00 ± 0.0 respectively).
3. We conclude that superoxide dismutase attenuates ischaemia—reperfusion-induced increases in albumin flux and hypoxic pulmonary vasoconstriction, and prevents consumption of linoleic acid in the isolated, blood-perfused rat lung.
Epoprostenol Increases Plasma Level of Atrial Natriuretic Peptide in humans
Authors: Nielsen C. B. , Bech J. N. , Pedersen E. B. 
Published: August 2015

1. In a placebo-controlled, randomized dose—response study the effect of the prostaglandin analogue epoprostenol (FlolanR) on the plasma level of atrial natriuretic peptide has been investigated in 14 healthy control subjects.
2. During epoprostenol infusion, atrial natriuretic peptide increased significantly in a dose-dependent manner, while it remained unchanged during placebo infusion [2 ng min−1 kg−1: epoprostenol 13.2% versus placebo −2.9%; 4 ng min−1 kg−1: epoprostenol 13.4% versus placebo −6.1%; 8 ng min−1 kg−1: epoprostenol 40.7% versus placebo −7.8% (medians), P &lt; 0.01 for all].
3. Mean blood pressure and heart rate increased significantly after epoprostenol, but were unchanged during placebo infusion [8 ng min−1 kg−1; mean blood pressure: epoprostenol −5.6% versus placebo 3.2%; heart rate: epoprostenol 32.7% versus placebo 3.1% (medians), P &lt; 0.01].
4. It is concluded that epoprostenol given intravenously increases the plasma level of atrial natriuretic peptide. The results support the hypothesis of an interaction between the prostaglandin system and atrial natriuretic peptide.
Respiratory Sinus Arrhythmia and Central Respiratory Drive in Humans
Authors: Al-Ani M. , Forkins A. S. , Townend J. N. , Coote J. H. 
Published: August 2015

1. The influence of central inspiratory drive on heart rate variability was investigated in young human subjects using power spectral analysis of R—R intervals.
2. The area of the high-frequency component occurring at the respiratory frequency (0.2–0.25 Hz) in the power spectral density curves was used as an index of respiratory sinus arrhythmia.
3. Central inspiratory drive was increased by breathing a CO2-enriched (5%) gas mixture and this condition was compared with a similar degree of ventilation produced voluntarily.
4. Tests were conducted on eight young subjects with and without low-dose scopolamine (scopoderm TTS) in a double-blind cross-over trial.
5. Scopolamine decreased heart rate and increased the high-frequency peak, suggesting that its main action on the cardiac vagal pathway was a peripheral one, possibly increasing the efficacy of vagal impulses on the cardiac pacemaker.
6. With scopolamine, CO2 breathing increased the area of the high-frequency component significantly more than a similar degree of ventilatory movements produced by voluntary hyperventilation.
7. It is concluded that respiratory sinus arrhythmia in humans is at least partly dependent on a central respiratory—cardiac coupling, most probably similar to that shown in animal studies.
Renal Denervation Prevents Sodium Retention and Hypertension in Salt-Sensitive Rabbits with Genetic Baroreflex Impairment
Authors: Weinstock Marta , Gorodetsky Elena , Kalman Ronald 
Published: August 2015

1. Rabbits with a genetic impairment in baroreflex control of heart rate become hypertensive on a high salt diet. The present study determined the effect of bilateral renal denervation on blood pressure and sodium balance after salt loading (four times normal intake; 28–36 mEq NaCl/day) in normotensive rabbits with high (Group I) and low (Group II) baroreflex sensitivity, respectively.
2. Eight rabbits in each group were denervated or sham-denervated 1 week before commencement of the high salt diet. Before operation, the two groups differed only in the gain of their cardiac baroreflex (Group I, −6.4 ± 0.4 beats min−1 mmHg−1; Group II, −3.2 ± 0.15 beats min−1 mmHg−1).
3. In Group I sham-denervated rabbits, mean arterial pressure remained unchanged, and plasma renin activity and heart rate fell significantly in response to the high salt. In Group II sham-denervated rabbits, mean arterial pressure increased by 10.6 ± 1.2 mmHg, and heart rate and plasma renin activity remained unchanged. Their cumulative Na+ retention and weight gain was more than twice that of Group I sham-denervated rabbits.
4. Renal denervation decreased plasma renin activity in both groups to &lt;1 pmol Ang I h−1 ml−1, lowered cumulative Na+ retention from 102 ± 4 to 35 ± 5 mEq (P&lt;0.01) and completely prevented the increase in mean arterial pressure in response to high salt in Group II.
5. The results suggest that Group II rabbits retain salt and fluid in response to their diet because of an abnormality in their control of renal nerve activity, possibly via vagal afferents. This results in blood pressure elevation because of an inability to lower peripheral resistance and heart rate in response to the increase in cardiac output.
6. Since they display several of the characteristics of salt-sensitive hypertensive humans, i.e. salt retention, normal plasma renin activity, but abnormal regulation of plasma renin activity and blood flow in response to salt loading, Group II are an appropriate model of human salt-induced hypertension.
Investigation by Polymerase Chain Reaction of Enteroviral Infection in Patients with Chronic Fatigue Syndrome
Authors: McArdle A. , McArdle F. , Jackson M. J. , Page S. F. , Fahal I. , Edwards R. H. T. 
Published: August 2015

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism.
2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio.
3. Fifty-eight percent of patients reported an uncharacterized ‘viral infection’ before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase).
4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.
β-Oxidation in Human Alcoholic and Non-Alcoholic Hepatic Steatosis
Authors: Eaton S. , Zaitoun A. M. , Record C. O. , Bartlett K. 
Published: August 2015

1. The CoA and carnitine ester intermediates of mitochondrial β-oxidation have not previously been quantified in liver disease, although there is some evidence that β-oxidation is inhibited in alcoholic fatty liver. Mitochondria were isolated from needle liver biopsies from normal subjects, from patients with alcoholic fatty liver and patients with fatty liver of other aetiologies, incubated with 60 μmol/l [U-14C]hexadecanoate and the resultant CoA and carnitine esters were measured.
2. Although there was no significant difference in β-oxidation flux between the patient groups, there was a significant rise in the proportion of 3-hydroxyacyl-CoA and 2-enoyl-CoA esters in patients with alcoholic fatty liver compared with normal subjects, and in patients with non-alcoholic fatty liver, suggesting an inhibition at the level of 3-hydroxyacyl-CoA dehydrogenase activity.
3. In alcoholic patients this difference could not be accounted for on the basis of the measured activity of short and long-chain 3-hydroxyacyl-CoA dehydrogenases, and it is suggested that either an inhibition of complex I activity or diminished amounts of ubiquinone are likely to be responsible for the observed accumulation of CoA and carnitine esters, which may contribute to the accumulation of triacylglycerols in alcoholic steatosis. In fatty liver of other aetiologies, short- and long-chain 3-hydroxyacyl-CoA dehydrogenase activities were decreased.
Beneficial Effects of L-Canavanine, a Selective Inhibitor of Inducible Nitric Oxide Synthase, during Rodent Endotoxaemia
Authors: Liaudet Lucas , Feihl François , Rosselet Anne , Markert Michèle , Hurni Jean-Marc , Perret Claude 
Published: August 2015

1. The cardiovascular failure in sepsis may result from increased nitric oxide biosynthesis, through the diffuse expression of an inducible nitric oxide synthase. In such conditions, nitric oxide synthase inhibitors might be of therapeutic value, but detrimental side effects have been reported with their use, possibly related to the blockade of constitutive nitric oxide synthase. Therefore, the use of selective inhibitors of inducible nitric oxide synthase might be more suitable. The aim of this study was to evaluate the effects of l-canavanine, a potentially selective inhibitor of inducible nitric oxide synthase, in an animal model of septic shock.
2. Anaesthetized rats were challenged with 10 mg/kg lipopolysaccharide intravenously. One hour later, they randomly received a 5 h infusion of either l-canavanine (20 mg h−1 kg−1, n = 15), nitro-l-arginine methyl ester (5 mgh−1 kg−1, n = 13) or 0.9% NaCl (2 ml h−1 kg−1, n = 21). Lipopolysaccharide induced a progressive fall in blood pressure and cardiac index, accompanied by a significant lactic acidosis and a marked rise in plasma nitrate. All these changes were significantly attenuated by l-canavanine, which also improved the tolerance of endotoxaemic animals to acute episodes of hypovolemia. In addition, l-canavanine significantly increased survival of mice challenged with a lethal dose of lipopolysaccharide. In contrast to l-canavanine, nitro-l-arginine methyl ester increased blood pressure at the expense of a severe fall in cardiac index, while largely enhancing lactic acidosis. This agent did not improve survival of endotoxaemic mice. In additional experiments, we found that the pressor effect of l-canavanine in advanced endotoxaemia (4 h) was reversed by l-arginine, confirming that it was related to nitric oxide synthase inhibition. In contrast, l-canavanine did not exert any influence on blood pressure in the very early stage (first hour) of endotoxaemia or in the absence of lipopolysaccharide exposure, indicating a lack of constitutive nitric oxide synthase inhibition by this agent.
3. In conclusion, l-canavanine produced beneficial haemodynamic and metabolic effects and improved survival in rodent endotoxic shock. The actions of l-canavanine were associated with a selective inhibition of inducible nitric oxide synthase and were in marked contrast to the deleterious consequences of nitro-l-arginine methyl ester, a non-selective nitric oxide synthase inhibitor, in similar conditions.
Carbohydrate Metabolism in Insulin Resistance: Glucose Uptake and Lactate Production by Adipose and Forearm Tissues in Vivo before and after a Mixed Meal
Authors: Coppack Simon W. , Fisher Rachel M. , Humphreys Sandy M. , Clark Mo L. , Pointon Jennifer J. , Frayn Keith N. 
Published: August 2015

1. To examine whether insulin resistance in vivo is manifest equally in both muscle and adipose tissues, we measured arteriovenous glucose and lactate fluxes across forearm (muscle) and abdominal subcutaneous (adipose) tissue in nine obese, glucose-intolerant subjects and 13 non-obese subjects of similar age and sex.
2. Compared with non-obese subjects, the forearm of the obese subjects was resistant to insulin stimulation of glucose uptake after a mixed meal. In contrast, adipose tissue showed little evidence of insulin stimulation of glucose uptake, and adipose tissue in subjects in both normal and obese groups behaved very similarly (assessed per 100 g of tissue).
3. For lactate flux, adipose tissue behaved very similarly (per 100 g of tissue) in obese and non-obese subjects, and was a consistent lactate exporter.
4. We conclude that insulin resistance of glucose uptake observed in the forearm of obese subjects is not evident in adipose tissue. Adipose tissue glucose uptake in obese, insulin-resistant subjects is similar to that in lean control subjects, although it occurs at elevated circulating insulin and glucose concentrations.
Luminal Epidermal Growth Factor Preserves Mucosal Mass of Small Bowel in Fasting Rats
Authors: Ulshen Martin H. , Raasch Ralph H. 
Published: August 2015

1. Fasting causes atrophy of small bowel mucosa which rapidly resolves with luminal feeding. This effect of enteral nutrient-5-be mediated by stimulation of growth factor secretion. We therefore evaluated whether luminal administration of epidermal growth factor, a peptide hormone found in gastrointestinal contents and trophic for small bowel mucosa, would prevent the mucosal atrophy associated with starvation.¡
2. Adult rats were: (i) fasted for 3 days, (ii) fasted and then refed for 1 day or (iii) fasted and then refed for 2 days. During the 2 days before study, animals in each group received infusions of epidermal growth factor (2.5 μg/day) or diluent alone into distal jejunum.
3. Epidermal growth factor treatment of fasted animals resulted in a tripling of mucosal ornithine decarboxylase activity (P&lt;0.001) and a doubling of mucosal DNA content (P&lt;0.001) in the jejunum, values similar to those of refed animals. Epidermal growth factor infusion in refed rats resulted in a further doubling of mucosal ornithine decarboxylase activity (P&lt;0.001), but no additional increase in DNA content. Effects of epidermal growth factor infusion were generally greater in jejunum than ileum.
4. In conclusion, luminal exposure to epidermal growth factor prevents starvation-induced mucosal atrophy in the small bowel, but does not enhance the mucosal growth associated with refeeding. Effects are greatest at the site of administration. Luminal epidermal growth factor is a potential mediator of the indirect effects of nutrient on mucosal growth in the small bowel. Enteral administration of epidermal growth factor holds promise for preventing atrophy and maintaining mucosal integrity in starved and post-operative patients.
Muscle Protein and Amino Acid Turnover in Rats in Vivo: Effects of Short-Term and Prolonged Starvation
Authors: De Blaauw I. , Deutz N. E. P. , Von Meyenfeldt M. F. 
Published: August 2015

1. Protein loss in muscle can be caused by decreased protein synthesis, increased breakdown or both. In small animals the tracer incorporation technique is mostly used to measure protein synthesis, but for degradation measurements in vitro or ex vivo settings are required. In human and large animal studies the arteriovenous dilution technique is used because it enables the measurement of synthesis and breakdown rates simultaneously. The applicability in small animals has not yet been proven. We used a starvation model to compare both techniques.
2. A primed constant infusion of l-[2,6-3H]phenylalanine was given to male Lewis rats after 16, 40, 64 and 112 h starvation. Protein synthesis rates of the gastrocnemius muscle were measured by the incorporation technique and compared with hindquarter protein turnover calculated in a two- and three-compartment arteriovenous dilution model.
3. Whole-body phenylalanine rate of appearance decreased from 456 ± 32 after 16 h to 334 ± 34 (nmol min−1 100 g−1 body weight) after 112 h starvation. Protein synthesis rates of the gastrocnemius muscle measured by the tracer incorporation technique decreased from 3.6 ± 0.4 after 16 h starvation to 2.2 ± 0.3 after 64 h starvation and 1.8 ± 0.4 (%/day) after 112h starvation. Hindquarter protein breakdown, calculated with the tracer dilution model, increased after 112 h starvation from 28 ± 12 to 77 ± 15 nmol min−1 100 g−1 body weight. Using the tracer dilution model, however, the calculated protein synthesis rate across the hindquarter also increased after prolonged starvation (29 ± 7 and 68 ± 16 nmol min−1 100 g−1 body weight after 16 and 112h respectively). In conjunction with this, calculated bidirectional membrane transport rates were also enhanced. Using valine and glutamine as tracers, the enhanced amino acid turnover rates were confirmed.
4. In conclusion, our results show that during short periods of starvation both methods give similar results. After prolonged starvation, however, an opposite change in disappearance rate and protein synthesis rate was observed. Assumptions made to calculate protein turnover using the arteriovenous dilution model may account for the discrepancy and care must be taken with the interpretation when using only one model in anaesthetized small animals.
Angiotensin Receptors in Myometrium and Myometrial Vessels from Uteri of Women during the Follicular and Luteal Phases of the Menstrual Cycle and in Late Pregnancy
Authors: Bing C. , Johnson I. R. , Pipkin F. Broughton 
Published: August 2015

1. Receptors for angiotensin II were identified and characterized in membrane fractions from myometrial samples obtained at non-pregnant hysterectomy in women of reproductive age. Specific binding was also measured in paired samples of vascular and ‘vessel-free’ myometrium.
2. A single class of high-affinity receptor sites was identified in the total myometrial preparations (n = 10), with a median equilibrium dissociation constant (Kd) of 0.122 nmol/l (range 0.065–0.465 nmol/l) and concentration of receptor sites (Bmax) of 149 fmol/mg protein (range 105–435 fmol/mg). Receptor characterization studies using losartan (an angiotensin type 1 receptor antagonist) and PD123177 (an angiotensin type 2 receptor antagonist) showed the myometrium to contain almost entirely type 2 receptors.
3. The median Kd and Bmax for specific angiotensin II binding in isolated myometrial vessel homogenates were 0.086 nmol/l (range 0.060–0.433) and 260 fmol/mg protein (range 197–737 fmol/mg) respectively. Vascular specific binding density was always higher in dissected out myometrial vessels than in paired vessel-free myometrium (median 372 compared with 120 fmol/mg protein; n = 20; P &lt; 0.001). The specific binding in the paired samples was strongly correlated (r = 0.8904, P &lt; 0.0001).
4. The specific binding of 125I-labelled angiotensin II in ‘vessel-free’ myometrium was higher in samples from the follicular phase than in samples from the luteal phase (median 144 compared with 37 fmol/mg; P &lt; 0.02). A similar trend was found in the vessels themselves, but this failed to reach statistical significance (459 compared with 225 fmol/mg; P = 0.051).
5. It is suggested that the down-regulation of the angiotensin type 2 receptors in the luteal (secretory) phase is a preparation for pregnancy, removing an inhibitory factor to uterine growth and vascularization and allowing greater prostacyclin synthesis.
Use of Continuous Haemofiltration to Assess the Rate of Lactate Metabolism in Acute Renal Failure
Authors: Wright D. A. , Forni L. G. , Carr P. , Treacher D. F. , Hilton P. J. 
Published: August 2015

1. Whole-blood lactate levels were measured at different rates of haemofiltration in 10 patients with acute renal failure undergoing conventional continuous haemofiltration using lactate-buffered replacement fluid.
2. The results enable both basal production rates and the metabolic clearance of lactate to be estimated in man.
Endogenous versus Exogenous Lithium Clearance for Evaluation of Dopamine-Induced Changes in Renal Tubular Function
Authors: Olsen Niels V. , Fogh-Andersen Niels , Strandgaard Svend , Leyssac Paul P. 
Published: August 2015

1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance (CLi) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo or 450 mg or 600 mg of lithium given in random order at 22.00 hours. After an overnight fast, renal clearance studies were performed during a 1 h baseline period and subsequently during the second hour of an infusion of 3 μg min−1 kg−1 of dopamine.
2. Baseline values of endogenous CLi and fractional excretion of lithium (FELi) [27.0 (23.5–30.5) ml/min and 24.2 (203–28.2)% (means with 95% confidence interval)] were lower than exogenous values [lithium, 450 mg: 32.7 (29.9–35.4) ml/min (P &lt; 0.05) and 27.4 (25.2–29.6)% (P &lt; 0.05); lithium, 600 mg: 33.4 (29.2–37.6) ml/min (P &lt; 0.05) and 28.6 (26.3–31.0)% (P &lt; 0.01)]. Both test doses of lithium increased the baseline sodium clearance (CNa), but glomerular filtration rate and urine flow rate remained unchanged.
3. Dopamine increased CNa to similar values on the three study days. CLi increased to 40.9 (35.5–46.5) ml/min (endogenous lithium, P &lt; 0.001), 43.2 (40.8–45.6) ml/min (450 mg of lithium, P &lt; 0.01) and 44.9 (41.3–48.4) ml/min (600 mg of lithium, P &lt; 0.001), respectively. FELi increased to 32.2 (27.5–37.0)% (P &lt; 0.01), 35.4 (33.0–37.7)% (P &lt; 0.01) and 35.9 (32.8–38.9)% (P &lt; 0.01), respectively. Values during dopamine infusion did not differ significantly.
4. The lower baseline values of endogenous CLi and FELi compared with exogenous values suggest that CLi in humans depends on the plasma concentrations of lithium. However, the effect of dopamine on CLi and FELi was expressed to the same extent with endogenous and exogenous lithium, indicating that the two methods are interchangeable for estimation of dopamine-induced changes in tubular function.