bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Synthesis in Isolated Enterocytes from Septic or Endotoxaemic Rats: Regulation by Glutamine
Authors: Higashiguchi Takashi , Noguchi Yoshifumi , Meyer Tory , Fischer Josef E. , Hasselgren Per-Olof
Published: August 2015

1. We studied the effect of sepsis and the regulation by glutamine of protein synthesis in enterocytes isolated from the small intestine of rats.

2. Sepsis was induced by caecal ligation and puncture; control rats were sham operated. Enterocytes were isolated from the jejunum and incubated in a medium containing [3H]phenylalanine.

3. Sixteen hours after caecal ligation and puncture, protein synthesis, measured as incorporation of radioactivity into protein, was increased by 65%, 89% and 137% respectively in enterocytes from the tips and mid-portions of the villi and from the crypts.

4. Addition of glutamine to incubated enterocytes stimulated protein synthesis in a dose-dependent manner, and this effect was most pronounced in crypt cells from septic rats. The effect of glutamine on protein synthesis was duplicated by equimolar concentrations of acetoacetate or 3-hydroxybutyrate, both of which may serve as fuel for enterocytes, and was blocked by the glutaminase inhibitor 6-diazo-5-oxo-l-norleucine.

5. The results suggest that sepsis stimulates protein synthesis in enterocytes and that glutamine regulates protein synthesis in the same cells, probably by energy provision.
Antecedent Hypoglycaemia in Non-Diabetic Subjects Reduces the Adrenaline Response for 6 Days but Does Not Affect the Catecholamine Response to other Stimuli
Authors: Robinson A. M. , Parkin H. M. , MacDonald I. A. , Tattersall R. B.
Published: August 2015

1. Recent hypoglycaemia reduces the counter-regulatory and symptomatic response to the next episode of hypoglycaemia. This study was designed to determine whether antecedent hypoglycaemia (a) affected the sympathoadrenal response to other stimuli (postural change and a mathematical stress test, (b) was associated with adaptation of cognitive function and (c) if avoided for 6 days led to the restoration of the counter-regulatory response to hypoglycaemia.

2. On the morning of day 1, 10 healthy men had their response to the sympathoadrenal stimuli assessed before an episode of hypoglycaemia (2.5 mmol/l). A further hyperinsulinaemia clamp was performed for 2 h (blood glucose 3.0 mmol/l or 5.0 mmol/l) in the afternoon and the assessments repeated the next day and 6 days later. Cognitive function using the four-choice reaction time test was assessed before and during the episodes of morning hypoglycaemia. The whole study was repeated 4 weeks later with the other afternoon glucose level.

3. Adrenaline levels and sweat rates were reduced (P < 0.05) on day 2 during hypoglycaemia on both occasions and had not returned to normal after 6 days. Symptom scores were lower (P < 0.05) only on day 2 after the afternoon of hypoglycaemia. The responses to the sympathoadrenal stimuli and cognitive function were unaffected by antecedent hypoglycaemia.

4. The adaptation of the counter-regulatory response to antecedent hypoglycaemia appears to be specific to hypoglycaemia. The response takes longer than 6 days but less than 4 weeks to return to normal. Antecedent hypoglycaemia does not lead to cerebral adaptation.
High-Affinity Interaction of Long-Chain Fatty Acids with Serum Albumin in Nephrotic Syndrome
Authors: Lerique Brice , Moulin Bruno , Delpero Claude , Purgus Rajsingh , Olmer Michel , Boyer Jean
Published: August 2015

1. We have examined the effect of hypoalbuminaemia, a hallmark of nephrotic syndrome, on the albumin—fatty acid equilibrium in the plasma of 11 adult patients with nephrosis compared with 12 healthy subjects and six subjects with normoalbuminaemic hyperlipoproteinaemia.

2. We used a dialysis exchange rate method which allows the evaluation in relative terms of the binding affinity of albumin for plasma fatty acid and the fatty acid availability, tentatively equated with the unbound fatty acid fraction.

3. In nephrotic patients, an increase (P < 0.001) in albumin affinity for fatty acid was seen compared with healthy subjects, which was negatively correlated with albuminaemia (r = −0.69, P < 0.02). No change in fatty acid availability was seen for the group as a whole, but individual values showed a wide scatter, with the highest values in four patients with the highest fatty acid-albumin molar ratios. The increase in albumin affinity for fatty acid was specific to nephrotic syndrome since no such effect was seen in subjects with hyperlipoproteinaemia, who only showed a moderate increase (P < 0.01) in fatty acid availability.

4. The increased albumin affinity for fatty acid in nephrotic syndrome supports the hypothesis that an albumin component with lower affinity for fatty acid might filter out through the diseased glomerular membrane and leave the high-affinity albumin in plasma.
Effects of Treadmill Exercise and High-Fat Feeding on Muscle Degeneration in Mdx Mice at the time of Weaning
Authors: Mokhtarian Asghar , Lefaucheur Jean Pascal , Even Patrick C. , Sebille Alain
Published: August 2015

1. Dystrophin-deficient hindlimb muscles of mdx mice undergo necrosis at the time of weaning when the motor activity of the mice greatly increases and muscle energy metabolism becomes more dependent on insulin and carbohydrates.

2. We have attempted to determine if the onset of myofibre necrosis in mdx mice at the time of weaning is related to the development of motor activity and/or the change in diet.

3. Fourteen-day-old mdx mice were divided into two groups after weaning. One group was trained to run on a treadmill and the other group was kept on a high-fat diet. Muscle necrosis was assessed histologically in the soleus and extensor digitorum longus muscles of mice in both experiments.

4. Keeping mice on a high-fat milk diet from the time of weaning up to 42 days of age did not influence the occurrence of necrosis in the soleus and extensor digitorum longus muscles of the mdx pups. In contrast, treadmill exercise greatly increased necrosis in both muscles.

5. We conclude that an increase in motor activity exacerbates the degeneration of hindlimb muscles of mdx mice at the time of weaning.
Microvascular Response to Tissue Injury and Capillary Ultrastructure in the Foot Skin of Type I Diabetic Patients
Authors: Rayman G. , Malik R. A. , Sharma A. K. , Day J. L.
Published: August 2015

1. Microvascular blood flow responses to injury and capillary ultrastructure were assessed by laser Doppler flowmetry and detailed light and electron microscopy respectively in skin biopsied from 28 patients with insulin-dependent diabetes and 17 control subjects.

2. The hyperaemic response induced by biopsy (P < 0.001) and heating to 44°C (P < 0.001) was significantly lower in the diabetic patients and showed progressive impairment with the severity of complications (P < 0.001).

3. Skin capillary basement membrane thickness was significantly increased in the diabetic patients (P < 0.001) and also increased with the severity of complications (P < 0.002). Both the luminal area (P < 0.001) and the endothelial cell outer perimeter (P < 0.002), measures of luminal and capillary size, respectively, were significantly reduced in all diabetic patients.

4. Basement membrane thickness was related significantly to the impaired hyperaemic response to both biopsy (P < 0.01) and thermal injury (P < 0.01).

5. Our findings support the hypothesis that structural abnormalities, which are characterized by an early reduction in capillary size and later thickening of basement membrane, form an important mechanism for the impaired hyperaemic response in diabetic patients.
Clinical Remission is Associated with Restoration of Normal High-Density Lipoprotein Cholesterol Levels in Children with Malignancies
Authors: Dessì Sandra , Batetta Barbara , Spano Ornella , Sanna Francesca , Tonello Mauro , Giacchino Mareva , Tessitore Luciana , Costelli Paola , Baccino Francesco M. , Madon Enrico , Pani Paolo
Published: August 2015

1. Serum lipids and lipoprotein profiles were determined in children affected by different types of malignancies (leukaemias or lymphomas and solid tumours) both before any treatment and after remission of the disease following chemical or surgical therapy.

2. At the time of diagnosis, children bearing tumours showed hypertriglyceridaemia and reduced concentrations of plasma high-density lipoprotein cholesterol levels, the decrease being particularly prominent in patients with haematological tumours. Children bearing solid tumours displayed an increase of total cholesterol, while those with haematological cancer showed decreased phospholipid levels; low-density lipoprotein cholesterol in neoplastic patients was not significantly different from control values. High triacylglycerol and low high-density lipoprotein cholesterol levels were also evident in cancer patients divided according to age into three groups (0–5, 6–10 and 11–15 years) when compared with age-matched control subjects. Similarly, high triacylglycerol and low high-density lipoprotein cholesterol levels were also observed in both male and female children when patients were divided according to sex and compared with corresponding controls.

3. Clinical remission after therapy was accompanied by an increase of high-density lipoprotein cholesterol levels compared with values observed at diagnosis. In contrast, post-treatment levels of triacylglycerol were higher than those observed before therapy. These results support the hypothesis that alterations of high-density lipoprotein cholesterol levels may be related, at least in part, to the rate of tumour growth, while modifications of triacylglycerol levels may be mediated by different mechanisms.
Intracolonic Release in Vivo of Interleukin-1β in Chronic Ulcerative Colitis
Authors: Casellas Francesc , Papo Michel , Guarner Francisco , Antolín María , Segura Rosa María , Armengol José Ramón , Malagelada Juan-Ramón
Published: August 2015

1. To investigate the role of interleukin-1β in chronic ulcerative colitis, we quantified interleukin-1β steady-state release into the colonic lumen.

2. We studied 26 patients with untreated chronic ulcerative colitis and seven patients with irritable bowel syndrome who served as disease controls. In seven ulcerative colitis patients, the disease was inactive and in 19 it was mild to moderately active, according to clinical and colonoscopic criteria. Seven patients with active colitis were studied before and after 4 weeks of treatment with oral 5-aminosalicylic acid.

3. Colonic perfusions were performed using a double-lumen technique. An isotonic solution was continuously infused 50 cm from the anal verge at 5 ml/min, and was recovered 30 cm distally by siphonage. Interleukin-1β was measured by ELISA, polymorphonuclear elastase by immunoactivation and leukotriene B4 by specific RIA.

4. All control patients and five out of seven patients with inactive colitis had undetectable interleukin-1β release. In active colitis, the release of interleukin-1β was detected in 17 out of 19 patients (median 500 pg/min, interquartiles 270–1582 pg/min, P < 0.01 compared with control subjects and patients with inactive colitis). Elastase and leukotriene B4 release were also significantly increased in active colitis compared with inactive colitis and controls. Leukotriene B4 release was similar in inactive colitis and controls, whereas elastase release was higher in inactive colitis than in controls. Five out of seven patients with colitis improved after treatment with 5-aminosalicylic acid. In all responder patients, interleukin-1β became undetectable or declined.

5. Our results demonstrate under conditions in vivo that active colitis is associated with enhanced interleukin-1β release into the colonic lumen whereas such release does not occur in remission, supporting the concept that ulcerative colitis flare-ups involve increased interleukin-1β production.
A Flow Cytometric Method to Measure Shape Change of Human Neutrophils
Authors: Cole A. T. , Garlick N. M. , Galvin A. M. , Hawkey C.J. , Robins R. A.
Published: August 2015

1. We report a flow cytometric method in which changes in forward angle light scatter are shown to correlate with microscopically evaluated shape change in stimulated human neutrophils. Neutrophil movement and chemotaxis is conventionally measured using Boyden chambers, which is a laborious and exacting technique. Microscopic scoring of neutrophil shape change has been shown to correlate well with Boyden chamber measurements, and although less laborious, still requires manual counting.

2. We now show that measurement of forward angle light scatter in a benchtop flow cytometer correlates closely with microscopic evaluation of neutrophil shape change in dose—response stimulation experiments with leukotriene B4, N-formyl-methionine-leucine-phenylalanine or interleukin-8. The relationship between shape change and increased forward angle light scatter was confirmed using the fluorescence-activated cell sorter to separate partially stimulated neutrophils, followed by reanalysis by flow cytometry and microscopic examination.

3. This flow cytometric method provides a convenient, rapid and objective measure of neutrophil responses to external stimuli.
Increased Inward Passive Permeability in Vitro to Sodium in Uraemic Erythrocytes
Authors: Corry Dalila B. , Ellis Charma C. , Tuck Michael L.
Published: August 2015

1. We have reported a normal sodium (Na) pump, but decreased loop-diuretic-sensitive Na efflux in erythrocytes from patients with chronic renal failure on haemodialysis, suggesting a different mode of co-transport in uraemia.

2. The present work extends these findings and examines in vitro simultaneous unidirectional and radiolabelled Na and K fluxes through the Na/K/Cl co-transport and the Na/K pump in washed erythrocytes from seven subjects with chronic renal failure and seven controls. Erythrocyte cytosolic calcium was also examined.

3. Ouabain-sensitive 86Rb influx was similar in patients and controls (1.76 ± 0.19 versus 1.72 ± 0.13 mmol h−1 litre−1 of erythrocytes) as was ouabain-sensitive 22Na efflux (3.62 ± 0.36 versus 4.04 ± 0.39 mmol h−1 litre−1 of erythrocytes).

4. Bumetanide-sensitive 86Rb and 22Na influx and 22Na efflux were measured at three concentrations (4, 8 and 12 mmol/l) of external K. In chronic renal failure, mean bumetanide-sensitive 22Na efflux was decreased at all external K concentrations compared with controls, and at physiological concentrations (4 mmol/l) external K was lower than controls (0.14 ± 0.01 versus 0.38 ± 0.05 mmol h−1 litre−1 of erythrocytes, P < 0.01). Mean bumetanide-sensitive 86Rb influx was also reduced in chronic renal failure at all external K concentrations, and at 4 mmol/l external K was lower than controls (0.13 ± 0.04 versus 0.34 ± 0.04 mmol h−1 litre−1 of erythrocytes, P < 0.01). Conversely, bumetanide-sensitive 22Na influx was markedly increased at all external K levels in chronic renal failure, and at 4 mmol/l external K values were elevated compared with controls (0.64 ± 0.18 versus 0.34 ± 0.04 mmol h−1 litre−1 of erythrocytes, P < 0.001). The mean cytosolic calcium concentration was higher in erythrocytes in chronic renal failure than controls (134.4 ± 8.6 versus 63.7 ± 5.8 nmol/l, P < 0.001).

5. Thus, in washed erythrocytes incubated in artificial media there is a markedly increased ouabain-insensitive Na influx in subjects with chronic renal failure which might be explained in part by the higher levels of cytosolic calcium. In vivo, this cell defect combined with suppression of the Na/K pump could lead to intracellular Na accumulation and play a role in uraemic complications.
Low Concentrations of Ouabain Increase Cytosolic Free Calcium Concentration in Rat Vascular Smooth Muscle Cells
Authors: Zhu Zhiming , Tepel Martin , Neusser Marcus , Zidek Walter
Published: August 2015

1. Low ouabain concentrations in the nanomolar range significantly increased cytosolic free calcium concentration.

2. The ouabain-induced cytosolic free calcium concentration increase was due to transplasmamembrane calcium influx, which could be prevented in the absence of extracellular calcium or by addition of the calcium channel blocker nifedipine.

3. The amount of stored cellular Ca2+, as determined by the thapsigargin-induced cytosolic free calcium concentration increase, was also enhanced by 1 nmol/l ouabain.

4. It is concluded that low ouabain concentrations affect intracellular cytosolic free calcium concentration homoeostasis.
Plasma Inhibitory Activity against Tumour Necrosis Factor in Fulminant Hepatic Failure
Authors: Keane Helen M. , Sheron Nick , Goka John , Hughes Robin D. , Williams Roger
Published: August 2015

1. Soluble tumour necrosis factor receptors released into the circulation inhibit the effects of excess tumour necrosis factor-α and represent an important protective response.

2. In this study we have measured the levels of tumour necrosis factor and soluble tumour necrosis factor receptors p55 and p75 in the plasma of 10 patients with fulminant hepatic failure and 10 healthy control subjects. The capacity of the plasmas at varying dilutions to inhibit the biological activity of 1000 pg/ml of recombinant tumour necrosis factor in a tumour necrosis factor cytotoxicity assay in vitro was also determined.

3. The mean plasma levels of tumour necrosis factor in patients with fulminant hepatic failure (48.4 ± 10.9 pg/ml) were significantly increased compared with normal control subjects (6.1 ± 1.04 pg/ml, P < 0.01). Plasma soluble tumour necrosis factor receptors p55 and p75 were also significantly elevated in patients with fulminant hepatic failure (18.16 ± 9.94 ng/ml and 16.06 ± 9.93 ng/ml respectively) when compared with normal control subjects (1.28 ± 0.24 ng/ml and 1.62 ± 0.91 ng/ml, P < 0.001).

4. Fulminant hepatic failure plasma had a much lower capacity to inhibit tumour necrosis factor bioactivity in vitro, with a statistically significant difference between the inhibitory capacity of the fulminant hepatic failure and normal plasma seen at plasma dilutions of 1:5 and 1:20 (P < 0.05).

5. The reduced tumour necrosis factor neutralization capacity observed in fulminant hepatic failure, despite the increased levels of soluble tumour necrosis factor receptors, suggests enhanced susceptibility to the potential deleterious effects of tumour necrosis factor in fulminant hepatic failure.
Thermoregulation and Heart Rate Variability
Authors: Fleisher Lee A. , Frank Steven M. , Sessler Daniel I. , Cheng Christi , Matsukawa Takashi , Vannier Carole A.
Published: August 2015

1. Heart rate variability is modulated by multiple control systems, including autonomic and hormonal systems. Long-term variability, i.e. the very low-frequency band of the power spectra, has been postulated to reflect thermoregulatory vasomotor control, based upon thermal entrainment experiments. However, the relationship between thermoregulatory responses (vasoconstriction and shivering) and heart rate variability has not been studied.

2. We performed two distinct protocols in a series of human subjects. In the first protocol, core temperature was reduced by intravenous infusion of cold saline, while skin temperature was unchanged. The second protocol involved skin-surface warming and cooling until shivering developed. Power spectral analysis was performed using a fast Fourier transformation, and the area in three distinct band-widths was determined.

3. Very low-frequency power (0.0039–0.04 Hz) increased significantly in response to core cooling, peripheral vasoconstriction and shivering, while both very low- and low- (0.04–0.15 Hz) frequency power increased in response to skin-surface cooling. Heart rate decreased during core cooling-induced vasoconstriction, suggesting a direct thermal response, and increased in relation to the metabolic demands associated with shivering.

4. Our results suggest that very low-frequency power is modulated by thermal stimuli which result in core hypothermia and thermoregulatory activity, while skin-surface cooling without core hypothermia does not selectively modulate this frequency band.
Haemodynamic Effects of Eating: The Role of Meal Composition
Authors: Høst U. , Kelbaek H. , Rasmusen H. , Court-Payen M. , Christensen N. Juel , Pedersen-Bjergaard U. , Lorenzen T.
Published: August 2015

1. The purpose of this study was to investigate the effect of fractional meal stimulation on postprandial haemodynamic changes, the possible correlation between these changes and the potential mediating role of circulating catecholamines and insulin.

2. Healthy young subjects were studied before and after ingestion of isocaloric, isovolumetric high-protein, carbohydrate or fat meals (80–85% of total energy), 60 kJ per kg of body weight. Multigated radionuclide cardiography with autologous 99mTc-labelled erythrocytes was performed for assessment of cardiac output, venous occlusion plethysmography to obtain forearm blood flow and Doppler-ultrasonography for portal vein flow. Plasma levels of catecholamines and insulin were determined by radioimmunoassay.

3. Cardiac output increased considerably after each meal, including the control meal (water) with only minor differences in extent and timing. Left ventricular volumes increased after food intake, most pronounced after carbohydrate and protein. Forearm blood flow increased only after carbohydrate and protein. Portal vein flow increased after all meals, especially after fat, but also after the control meal. There was a significant correlation between the increment in cardiac output and changes in forearm and portal vein flow, but no correlation between either haemodynamic response and plasma catecholamines or insulin.

4. Postprandial cardiovascular changes are not substantially different after various isocaloric and isovolumic meal compositions. Gastric distension seems to play a role in the increase in cardiac output, accomplished by ventricular dilatation. These changes seem to some extent to be linked to changes in muscle and splanchnic flow.
Differential Effects of Low- and High-Intensity Lower Body Negative Pressure on Noradrenaline and Adrenaline Kinetics in Humans
Authors: Jacobs Marie-Cecile , Goldstein David S. , Willemsen Jacques J. , Smits Paul , Thien Theo , Lenders Jacques W. M.
Published: August 2015

1. Lower body negative pressure provides a means to examine neurocirculatory reflexive responses to decreases in venous return to the heart. We assessed whether the pattern of catecholaminergic responses to lower body negative pressure depends on the intensity of the stimulus (−15 versus −40 mmHg).

2. In 14 healthy subjects, responses of forearm blood flow and noradrenaline spillover and of total body noradrenaline and adrenaline spillover were assessed during infusion of [3H]noradrenaline and [3H]adrenaline during −15 and −40 mmHg of lower body negxative pressure.

3. During lower body negative pressure at −15 mmHg, heart rate and pulse pressure did not change, but forearm vascular resistance increased by 25–50%. Forearm noradrenaline spillover increased by about 50%, from 0.63 ± 0.16 to 0.94 ± 0.23 pmol min−1 100 ml−1 (P<0.05). Total body noradrenaline spillover did not change, and total body adrenaline spillover increased significantly by about 30%. Clearances of noradrenaline and adrenaline were unchanged.

4. During lower body negative pressure at −40 mmHg, heart rate increased and pulse pressure decreased. Forearm vascular resistance increased by about 100%, and forearm noradrenaline spillover increased by 80%, from 0.73 ± 0.19 to 1.32 ± 0.36 pmol min−1 100 ml−1 (P<0.05). Total body noradrenaline spillover increased by 30%, and total body adrenaline spillover increased by about 50%. Clearances of both noradrenaline and adrenaline decreased.

5. The results are consistent with the view that selective deactivation of cardiopulmonary baroreceptors during low-intensity lower body negative pressure increases sympathoneural traffic to forearm skeletal muscle and increases adrenomedullary secretion without a concomitant generalized increase in sympathoneural outflows. Concurrent deactivation of cardiopulmonary and arterial baroreceptors during high-intensity lower body negative pressure evokes a more generalized increase in sympathoneural activity, accompanied by further increased adrenomedullary secretion and decreased plasma clearances of noradrenaline and adrenaline. The findings support differential increases in skeletal sympathoneural and adrenomedullary outflows during orthostasis, with more generalized sympathoneural responses to systemic hypotension.
Nitric Oxide in Streptozotocin-Induced Diabetes Mellitus in Rats
Authors: Maree Abed , Peer Gari , Iaina Adrian , Blum Miriam , Wollman Yoram , Csernihovsky Tamara , Silverberg Donald S. , Cabili Shaltiel
Published: August 2015

1. The present study was performed to determine the relationship between diabetic glomerular hyperfiltration and nitic oxide as modulated by the chronic administration of l-arginine and/or N-ω-nitro-l-arginine, a known nitric oxide synthase inhibitor in streptozotocin-induced diabetic rats.

2. Normal rats and rats drinking hypertonic glucose (10%) were used as time-controlled groups. Six weeks after administration of streptozotocin the diabetic rats had significantly higher creatinine clearance (667 ± 53 μl min−1 100 g−1 body weight) than before and streptozotocin (456 ± 38 μl min−1 100 g−1 body weight, P<0.005) and very high plasma (37.8 ± 10.9 μmol/l) and urinary (3.492 ± 0.179 nmol min−1 100 g−1 body weight) nitrite + nitrate (stable metabolites of nitric oxide) values compared with before streptozotocin administration [19.3 ± 2.8 μmol/l (P<0.001) and 0.420 ± 0.051 nmol min−1 100 g−1 body weight (P<0.001) respectively]. The 6-week diabetic rats had higher systolic blood pressure (124.2 ± 2.9 mm Hg, P<0.05) than before streptozotocin (108 ± 8 mmHg), but had a value similar to that of the hypertonic-glucose-drinking rats.

3. The diabetic rats supplemented with l-arginine did not show an increase in creatinine clearance and had a lower urinary excretion of nitrite + nitrate (0.999 ± 0.27 nmol min−1 100 g−1 body weight, P<0.005) than the respective untreated streptozotocin-induced diabetic rats. Creatinine clearance increased in the normal and glucose-drinking rats that received l-arginine. The administration of l-arginine resulted in significant reduction in blood pressure in all groups studied. The chronic nitric oxide synthase inhibitor resulted in high blood pressure, and in a significant decrease in creatinine clearance and urinary nitrite + nitrate excretion in all groups studied. In both diabetic and glucose-drinking rats, the l-arginine therapy resulted in significantly lower plasma and urinary glucose levels than in their respective untreated control groups.

4. The nitric oxide synthase inhibitor increased the plasma and urinary glucose concentration in both diabetic and glucose-drinking rats.

5. Our results indicate that diabetic rats are characterized by high plasma concentrations and elevated urinary excretion of nitrite + nitrate, suggesting a state of high nitric oxide production. The vascular response to nitric oxide in diabetic rats may be different at the glomerular and peripheral vascular bed.
Fasting Increases the Extent of Muscle Necrosis in the mdx Mouse
Authors: Helliwell T. R. , MacLennan P. A. , McArdle A. , Edwards R. H. T. , Jackson M. J.
Published: August 2015

1. The effects of fasting for 48 h were investigated in CS7BL/10 (wild type) and age-matched C57BL/10 dystrophin-deficient (mdx) mice.

2. Fasting resulted in an increased percentage of necrotic fibres in muscles from the hindlimb and lumbar regions of mdx mice. The percentage of necrotic fibres of forelimb and chest muscles of mdx mice was unaltered by fasting. In wild-type mice, very few necrotic fibres were observed after fasting.

3. The necrotic changes in fasted mdx muscle were not accompanied by altered energy status as evaluated by muscle ATP and phosphocreatine concentrations.

4. A significantly decreased rectal temperature was observed in mdx but not in wild-type mice after fasting.

5. Fasting would normally be expected to cause a reduction in muscle fibre size. The high prevalence of necrosis in fasted mdx mice is therefore an unusual response that may be related to disturbance of the mechanisms which, in the fed state, compensate for the dystrophin deficiency in these animals.
Effects of Facial Cooling on Elderly and Young Subjects: Interactions with Breath-Holding and Lower Body Negative Pressure
Authors: Collins K. J. , Abdel-Rahman T. A. , Easton J. C. , Sacco P. , Ison J. , Doré C. J.
Published: August 2015

1. The effects of convective facial cooling by cold air on arterial blood pressure, heart rate and finger blood flow and on the reflex interactions between facial cooling and respiratory and orthostatic cardiac reflexes have been examined in 28 young adults (20–39 years) and 17 elderly (66–78 years) volunteer subjects.

2. During 2 min facial cooling alone, bradycardia was smaller (P < 0.001) and reduction in finger blood flow smaller (P < 0.001) in elderly subjects than in young subjects. Increases in systolic blood pressure and mean arterial pressure were similar and diastolic pressure increased only in the young subjects. Systolic blood pressure and mean arterial pressure remained elevated in the elderly 1 min after facial cooling, but subsided in the young.

3. Arterial blood pressure increased more during a 30-s breath-hold in expiration than in inspiration (P < 0.001) in both groups, and this was exaggerated by breath-hold in expiration combined with facial cooling. The bradycardia produced by facial cooling and breath-holding in expiration was more pronounced in the young subjects than in the elderly (P < 0.002).

4. Interactions between facial cooling and orthostatic reflexes induced by lower-body negative pressure showed significantly different age-related linear trends. Facial cooling diminished the hypotension induced by lower-body negative pressure in both groups. Facial cooling had a greater effect in diminishing the lower-body negative pressure-induced tachycardia in the young than in the elderly.

5. The mechanism of alteration of the facial cooling response in elderly subjects could be largely impairment of arterial baroreflexes, particularly as a result of reduced cardiac vagal activity as well as impairment of cardiopulmonary reflexes with ageing.
Smooth Muscle-Derived Nitric Oxide is Elevated in Isolated Forearm Veins in Human Alcoholic Cirrhosis
Authors: Ryan Jeremy , Jennings Garry , Dudley Frank , Chin-Dusting Jaye
Published: August 2015

1. Cirrhosis is often complicated by disturbances in the systemic circulation. We have previously demonstrated decreased vascular responses to vasoconstrictors in forearm resistance arteries in subjects with alcoholic cirrhosis. In the current study we investigate the role of the potent endogenous vasodilator nitric oxide in the peripheral circulation of these patients.

2. Ten patients with alcoholic cirrhosis (Pugh grade A) and 10 age-matched control subjects were studied. The effect of blockade of nitric oxide synthesis was studied both in vivo in forearm resistance arteries using forearm venous occlusion plethysmography and in vitro in veins isolated from the forearm. The role of endothelium-derived nitric oxide was studied in vivo using the endothelium-dependent vasodilator acetylcholine.

3. Mean arterial pressure and forearm basal flow in vivo were similar in the two groups. The constrictor response (percentage decrease in forearm blood flow) to noradrenaline (100 ng/min) was 26% smaller in patients with cirrhosis (31.65 ± 2.64%) than in control subjects (42.75 ± 3.87%, P = 0.037). Constrictor responses to the nitric oxide synthase inhibitor NG-monomethyl-l-arginine were not different in the two groups. Dilator responses to acetylcholine were significantly attenuated in cirrhotic patients compared with control subjects.

4. To investigate the role of smooth muscle-derived nitric oxide in vitro, all veins were stripped of their endothelium. Responses to noradrenaline were significantly diminished in veins isolated from patients with cirrhosis compared with control subjects. Incubation with the nitric oxide synthase inhibitor Nω-nitro-l-arginine had no effect on responses to noradrenaline in veins from control subjects but significantly enhanced the maximal response to noradrenaline by 23.95% (range 3.77–100%, P = 0.043) in veins from patients with cirrhosis.

5. Responses to noradrenaline were attenuated in vivo in forearm resistance arteries in patients with alcoholic cirrhosis. This impairment was also apparent in forearm isolated veins, stripped of the endothelium. Our data exclude a major role for endothelium-derived nitric oxide but highlight a possible role for smooth muscle-derived nitric oxide.
Determination of Protein Synthesis in Lymphocytes in Vivo after Surgery
Authors: Essén Pia , McNurlan Margaret A. , Thorell Anders , Tjäder Inga , Caso Giuseppe , Anderson Susan E. , Wernerman Jan , Garlick Peter J.
Published: August 2015

1. The stimulation and depression of peripheral blood lymphocytes has previously been studied in vitro, showing an immune depression postoperatively; however, it is difficult to interpret these in vitro findings. Therefore, an in vivo technique has been established for determination of the fractional protein synthesis rate, as an index of metabolic activity in human peripheral blood lymphocytes, by using a stable isotope technique.

2. The rate of protein synthesis was calculated from the increase in enrichment of l-[2H5]phenylalanine in protein of a mixed population of mononuclear leucocytes, isolated by density gradient, after an intravenous flooding dose of l-[2H5]phenylalanine. A linear time course of isotopic incorporation into the cells was demonstrated.

3. The fractional rate of protein synthesis of a mixed population of mononuclear leucocytes was studied in relation to surgical interventions and to potential modifiers of the response. The fractional synthesis rate increased 24 h after open and laparoscopic cholecystectomy (49 ± 19% and 40 ± 14% respectively, P > 0.02), irrespective of postoperative total parenteral nutrition or preoperative glucose infusion. In contrast to surgery, insulin did not stimulate protein synthesis in peripheral mononuclear leucocytes.
Sex Differences in Correlates of Steady State and Pulsatile Component of Blood Pressure
Authors: Scuteri A. , Cacciafesta A. M. , Di Bernardo M. G. , De Propris A. M. , Recchi D. , Celli V. , Idone G. , Nocco M. L. , Marigliano V.
Published: August 2015

1. The aim of the present study was to evaluate whether metabolic factors are linked to the steady component and the pulsatile component of blood pressure, evaluated as mean arterial pressure and pulse pressure respectively, in a sex-specific manner. 2. A cohort of 299 subjects (152 males, 147 females; 25–80 years of age) was studied. Patients presenting congestive heart failure, coronary insufficiency, severe valvular heart disease, neurological accident in the last 6 months, renal or respiratory failure, cancer, diabetes mellitus or acute infectious disease were excluded. None of the women was taking oral contraceptives or oestrogen supplementation. All cardioactive drugs were withdrawn at least 2 weeks before the subjects entered the study.

3. Men presented higher mean arterial pressure (120 ± 15 compared with 115 ± 16 mmHg, P < 0.01) and lower pulse pressure values (63 ± 16 compared with 67 ± 18 mmHg, P < 0.05) than women. In men, no significant relation between mean arterial pressure and the tested variables was detected; multiple regression analysis demonstrated that age contributed independently to the model for pulse pressure with a multiple r2 of 0.10 (P < 0.01). In women, body mass index contributed independently to the model for mean arterial pressure, with a multiple of 0.12 (P < 0.005); age and, to a lesser extent, body mass index, glycaemia and triglyceridaemia persisted as independent determinants of pulse pressure at the multiple regression analysis, with a multiple r2 of 0.20 (P < 0.001).

4. Our findings suggest that metabolic risk factors are associated differently with pulse pressure and mean arterial pressure values in the two sexes.
Augmented Thermic Effect of Amino Acids under General Anaesthesia Occurs Predominantly in Extra-Splanchnic Tissues
Authors: Selldén Eva , Bränstróam Robert , Brundin Tomas
Published: August 2015

1. Intravenous infusion of amino acid mixtures stimulates human oxidative heat production more effectively under general anaesthesia than in the unanaesthetized state. To analyse the splanchnic and extra-splanchnic regional distribution of this stimulation, whole body and splanchnic oxygen uptake, blood flow and blood temperatures were measured by a catheterization technique in 14 patients undergoing isoflurane anaesthesia for abdominal surgery. During the anaesthesia period, a mixture of 19 amino acids (240 kJ/h) was infused intravenously into seven of the patients while the others served as controls, receiving isovolumic infusions of a nutrient-free saline solution.

2. Whole body oxygen consumption fell by ≈ 40% during anaesthesia and surgery in the controls. Approximately 80–95% of the reduction occurred in the extra-splanchnic tissues. The splanchnic oxygen uptake fell by 31 ± 6% in the controls during the initial phase of anaesthesia, after which it returned to the pre-anaesthesia level. The initial reduction of the controls' splanchnic oxygen consumption accounted for only ≈23% of the simultaneous anaesthesia-induced reduction in pulmonary oxygen uptake. No initial reduction of the splanchnic oxygen uptake was observed in the patients treated with amino acid.

3. The amino acid infusion stimulated the whole body oxidative heat production by ≈18 W during anaesthesia and surgery and by ≈70 W at the emergence from anaesthesia. Approximately 74% of the stimulation occurred in the extra-splanchnic tissues. At awakening, the splanchnic oxygen uptake rose to ≈64% above the pre-anaesthesia level in the amino acid group.

4. During the entire period of anaesthesia, the whole body heat content fell by 282 ± 68 kJ in the controls and by 57 ± 25 kJ in the amino acid group. Amino acid treatment thus prevented ≈80% of the anaesthesia-induced reduction in whole body heat content.

5. During anaesthesia and surgery, cardiac output was ≈25% and ≈6% below the baseline, pre-anaesthesia levels in the control and amino acid groups, respectively. At awakening, it rose to ≈44% above baseline in the amino acid group while in the controls it remained unchanged. In both groups the splanchnic blood flow was unaffected by anaesthesia or by amino acid infusions.
Time Course Study of Oxidative Stress in Aorta and Heart of Diabetic Rat
Authors: Kakkar Rakesh , Mantha Subrahmanyam V. , Kalra Jawahar , Prasad Kailash
Published: August 2015

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level [thiobarbituric acid-reactive substances (TBARS)] and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in aorta, heart and blood of control and streptozotocin-induced diabetic rats at various stages of development of diabetes (0 to 6 weeks).

2. There was no change in the TBARS levels of aorta, heart and blood in the control group. A significant (P < 0.05) increase in TBARS levels of aorta, heart and blood was observed in the diabetic group.

3. There were no significant changes in the activities of superoxide dismutase, catalase and glutathione peroxidase in the aorta, heart and blood of control rats at all time intervals. In the diabetic group, there was a significant (P < 0.05) increase in the activity of superoxide dismutase and glutathione peroxidase in aorta from the fourth week onwards while the activity of catalase increased at all time intervals. In the heart of diabetic rats, the activity of total superoxide dismutase and Cu—Zn-superoxide dismutase increased significantly (P < 0.05) from the second week onwards while activity of Mn-superoxide dismutase decreased at the fourth week and increased at the sixth week. The activity of catalase and glutathione peroxidase increased significantly (P < 0.05) at all time intervals. In the blood, the activity of superoxide dismutase and glutathione peroxidase increased from the third week while catalase activity increased from the fourth week.

4. The present findings suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively.
Validation of the Supine Venous Pump Function Test: A New Non-Invasive Tool in the Assessment of Deep Venous Insufficiency
Authors: Janssen M. C. H. , Claassen J. A. H. R. , Van Asten W. N. J. C. , Wollersheim H. , De Rooij M. J. M. , Thien TH.
Published: August 2015

1. A new non-invasive test was developed to assess calf muscle pump function: the supine venous pump function test. The technique uses strain-gauge plethysmography and is performed in the supine position. The method is superior to other non-invasive methods because basically the most essential haemodynamic parameter, venous pressure decrease, is used by properly converting venous volume measurements into venous pressure. The validity of this test was established by comparison with invasive venous pressure measurements and by determining the reproducibility. Additionally, normal values were determined.

2. In 28 extremities the supine venous pump function test was performed simultaneously with invasive venous pressure measurements. The reproducibility of the test was assessed in 10 randomly chosen volunteers. In 34 volunteers normal values were obtained and 26 patients with clinical venous insufficiency were examined.

3. Comparison of the two methods revealed a correlation coefficient of r = 0.98 (P < 0.001). A mean difference of 3.9%pf between both methods was found with limits of agreement of − 6.3%pf to 14.1%pf. The coefficient of repeatability was 13%pf and the coefficient of variation was 9%. The normal range was found to be >60%pf. The mean pump function in the patient group was 45%pf.

4. The limits of agreement are small enough to be confident that the supine venous pump function test can be used instead of invasive venous pressure measurements to assess calf muscle pump function in clinical practice. The reproducibility of the test is good.
Cerebral Oxidative Metabolism in Hypertension
Authors: Dickinson C. John
Published: August 2015

1. The evidence is now overwhelming that so-called ‘essential’ hypertension in man, i.e. high systemic arterial pressure for no apparent cause, is commonly initiated by increased efferent sympathetic activity directed to the cardiovascular system. Eventually structural and other changes take place in the heart, kidneys and blood vessels. These may reinforce, augment and even conceal the initially neurogenic background. The cause of the increased sympathetic activity remains in dispute, but it is probably not psychological in most cases.

2. The brain has a high requirement for energy — twice that of the heart, at rest. In the normotensive adult, the brain's needs are met almost exclusively by the oxidation of glucose. This results in a cerebral respiratory quotient for the brain of approximately unity. The brain can utilize other materials, notably ketones, as it does to a considerable extent in the fetus. It retains this capability in adult life, even though normal adults do not make use of it.

3. In human hypertension the cerebral respiratory quotient falls in proportion to the rise of arterial pressure, indicating the consumption of other fuels in addition to glucose. β-Hydroxybutyrate is certainly one of these, but fatty acids may also be utilized.

4. A similar or greater reduction of cerebral respiratory quotient than in essential hypertension is seen in chronic cerebrovascular disease and in chronic heart failure in man. This raises the possibility that although cerebral blood flow is only slightly reduced in hypertensive patients at rest, the cerebral circulation is potentially under threat. The change in the pattern of oxidative metabolism may be looked upon as an adaptation to the threat. This would fit in with strong epidemiological and pathological evidence linking hypertension with cerebral, especially vertebrobasilar, atheroma.

5. Many of the pathophysiological changes in essential hypertension have parallels in the spontaneous hypertensive rat and its stroke-prone variant. Such rats have an impaired cerebral blood supply. Infarctions are easily produced by arterial occlusions which have little adverse effect on Wistar—Kyoto rats. Spontaneous hypertensive rats and stroke-prone spontaneous hypertensive rats also have reduced cerebral glucose utilization, which mirrors the situation in essential hypertension.

6. The Cushing response — threatened medullary ischaemia activating sympathetic vasomotor efferent nerves — could provide the mechanism by which chronic borderline or intermittent cerebral circulatory inadequacy passed a signal to activate sympathetic efferent nerves, either directly or through altered brain metabolism.

7. Other interpretations are possible, but the evidence of this review suggests that further investigation of cerebral oxidative metabolism in hypertension and in related conditions may shed light on the still elusive aetiology of essential hypertension.
Impaired Endothelium-Dependent and Independent Dilatation of Forearm Resistance Arteries in Men with Diet-Treated Non-Insulin-Dependent Diabetes: Role of Dyslipidaemia
Authors: Watts G. F. , O'brien S. F. , Silvester W. , Millar J. A.
Published: August 2015

1. We measured endothelium-dependent and independent dilatation of forearm resistance arteries in 29 men with diet-treated non-insulin-dependent diabetes mellitus and 18 age- and sex-matched control subjects. None of the diabetic patients had hypercholesterolaemia, overt hypertension or microproteinuria.

2. We examined endogenous and exogenous nitric oxide-mediated vasodilatation by measuring forearm blood flow with venous occlusive plethysmography after administration of acetylcholine (7.5 and 15 μg/min) and sodium nitroprusside (3 and 10 μg/min), respectively, into the brachial artery. NG-monomethyl-l-arginine was also infused to study the inhibition of basal and stimulated release of nitric oxide.

3. The vasodilatory response to acetylcholine, expressed as area under curve, was significantly decreased in the diabetic patients compared with the control subjects (P = 0.019). NG-monomethyl-l-arginine significantly reduced basal (P < 0.001) and acetylcholine-stimulated blood flow (P < 0.02) in both groups. The vasodilatory response (also expressed as area under curve) to sodium nitroprusside was significantly less (P = 0.044) in the diabetic patients than in the control subjects.

4. In the diabetic patients, impaired vasodilatory responses to acetylcholine were significantly correlated with higher serum triacylglycerols (P = 0.048) and lower high-density lipoprotein-cholesterol concentrations (P = 0.007); the association with high-density lipoprotein was independent of age, glycated haemoglobin and blood pressure. Sodium nitroprusside responses were not correlated with lipid and lipoprotein concentrations.

5. We conclude that there is impaired endothelial and smooth muscle cell function in men with diet-treated non-insulin-dependent diabetes mellitus uncomplicated by overt hypertension or microproteinuria. Endothelial dysfunction may be related to diabetic dyslipidaemia and associated metabolic disturbances.