bluuebunny/crossref_metadata_2025 huggingface dataset:
Ketone infusion lowers hormonal responses to hypoglycaemia: Evidence for acute cerebral utilization of a non-glucose fuel
Authors: Amiel Stephanie A. , Archibald Helen R. , Chusney Gary , Williams Alistair J. K. , Gale Edwin A. M.
Published: August 2015

1. The effect of hyperketonaemia on counter-regulatory hormone responses to hypoglycaemia has been examined in six healthy subjects.

2. A controlled, step-wise reduction in blood glucose concentration was achieved by adjusting the rate of glucose infusion during a primed-continuous infusion of soluble insulin (1.5 m-units min−1 kg−1 body weight, plasma insulin concentration approximately 90 m-units/l). Simultaneous infusion of either saline or β-hydroxybutyrate (3 mg min−1 kg−1 body weight) was administered in a single-blind fashion, in random order. Despite a need for 40% more glucose during the ketone infusion, an identical fall in blood glucose concentration was achieved in each study.

3. The glycaemic threshold for stimulating an adrenaline response of 0.41 nmol/l was reduced from 3.1 to 2.8 mmol/l (P < 0.05) during ketone infusion, and that for stimulating a response of more than 50% of basal from 3.6 to 3.1 mmol/l (P < 0.001). The peak adrenaline response fell from 7.97 to 2.6 nmol/l (P < 0.04). Peak noradrenaline, cortisol and growth hormone responses were also significantly lower during ketone infusion (P = 0.04, 0.001 and 0.006, respectively). Glucagon responses alone were unaffected by hyperketonaemia.

4. The provision of an alternate metabolic fuel thus produced immediate changes in the neurohumoral responses to hypoglycaemia. This is consistent with the hypothesis that human nervous tissue can metabolize ketones acutely.
Altered small-intestinal permeability associated with diarrhoea in human-immunodeficiency-virus-infected Caucasian and African subjects
Authors: Kapembwa M. S. , Fleming S. C. , Sewankambo N. , Serwadda D. , Lucas S. , Moody A. , Griffin G. E.
Published: August 2015

1. Small-intestine integrity in Caucasian and African patients infected with human immunodeficiency virus was determined by measuring the permeation across the mucosa of two sugars, lactulose and mannitol.

2. The sugars were assayed by h.p.l.c. and pulsed amperometric detection in 6 h urine samples. Stool microscopy for enteropathogens was performed in all patients.

3. The ratio of lactulose to mannitol recovered in urine was increased in Caucasian and African patients with advanced human immunodeficiency virus infection. Asymptomatic human-immunodeficiency-virus-infected subjects had a normal lactulose/mannitol ratio. African patients with diarrhoea showed a twofold reduction in mannitol excretion. Such a change in mannitol absorption was not detected in Caucasian patients and occurred regardless of the presence of enteropathogens.

4. Altered small-intestinal permeability is associated with symptomatic diarrhoea in human immunodeficiency virus infection in both Caucasian and African patients.
Heparin and heparan sulphate are inhibitors of human leucocyte elastase
Authors: Walsh R. L. , Dillon T. J. , Scicchitano R. , McLennan G.
Published: August 2015

1. Heparin and heparan sulphate strongly inhibited human leucocyte elastase activity in an automated assay using the soluble substrate, n-succinyl-(l-alanine)3-p-nitroanilide (50% inhibition of 250 μl of 10 μg of human leucocyte elastase/ml was obtained with 80 μl of 2.8 μg of heparin/ml and 8 μg of heparan sulphate/ml). Less significant inhibition at the same concentrations was seen with the other glycosaminoglycans tested: hyaluronic acid and chondroitin sulphates A–C.

2. Heparin and heparan sulphate also strongly inhibited human leucocyte elastase activity towards insoluble human lung elastin, as determined by an e.l.i.s.a. for soluble elastin-derived peptides released by elastolytic activity on the elastin. This inhibition was shown not to be due to a direct interference of the glycosaminoglycans in the e.l.i.s.a. nor to the inhibition causing a change in the size of the elastin-derived peptides. However, unlike the chromogenic assay with n-succinyl-(l-alanine)3-p-nitroanilide as substrate, where heparin was the more effective inhibitor, in this assay system heparan sulphate was the more effective inhibitor (50% inhibition of 100 μl of 50 ng of human leucocyte elastase/ml was obtained with 100 μl of 4.5 μg of heparin/ml and 0.8 μg of heparan sulphate/ml). These results suggest that heparin and heparan sulphate, as components of cellular and basement membranes, are likely to have a role in protecting structural proteins, such as elastin, from the proteolytic activity of human leucocyte elastase.

3. The degree of inhibition by heparin was independent of pH within the range of pH studied (pH 6–9) and was almost immediate in the automated chromogenic assay system where a 10 s preincubation step was used. The inhibitory effect of heparin could be prevented by the addition of protamine sulphate or by the removal of heparin by an ion-exchange resin.

4. Low Mr preparations of heparin were also found to inhibit human leucocyte elastase, although preparations with Mr of 2000 or less did not inhibit the enzyme to the same extent as commercial preparations.

5. Heparin at the same concentrations did not inhibit other leucocyte enzymes, such as cathepsin G and myeloperoxidase, nor the pancreatic enzymes, pancreatic elastase, trypsin and chymotrypsin.
Non-diabetic microalbuminuria in clinical practice and its relationship to posture, exercise and blood pressure
Authors: West J. N. W. , Gosling P. , Dimmitt S. B. , Littler W. A.
Published: August 2015

1. The effects of posture and exercise on the relationship between low-level urinary albumin excretion (microalbuminuria) and blood pressure was investigated in two groups of non-diabetic patients at increased cardiovascular risk: 21 otherwise healthy patients with untreated essential hypertension (blood pressure > 160/90 mmHg), and 14 age-matched patients with blood pressure at presentation within the normotensive range (< 160/90 mmHg) attending a cardiovascular clinic for assessment of chest pain.

2. A significant linear relationship between logarithmically transformed ‘spot’ urinary albumin/creatinine ratio and simultaneous clinic blood pressure existed when data from both groups of patients were analysed (r = 0.58, P < 0.05). The relationship between the scatter plot of blood pressure and the albumin/creatinine ratio appeared most marked when the mean blood pressure exceeded 120 mmHg.

3. In patients with essential hypertension, clinic systolic blood pressure was related to the albumin/creatinine ratio in simultaneous ‘spot’ urine samples (r = 0.69, P < 0.05) and also to the albumin/creatinine ratio in early-morning urine samples (r = 0.51, P < 0.05). However, the relationship between clinic blood pressure and simultaneous ‘spot’ urinary albumin/creatinine ratio in the patients with chest pain did not achieve significance when analysed independently.

4. Hourly averaged ambulatory intra-arterial blood pressure was recorded in four of the patients with essential hypertension during normal daytime activity, and a significant correlation with the simultaneous hourly daytime urinary albumin/creatinine ratio was found (r = 0.65, P < 0.01).

5. Low-level albumin excretion increased in both groups after exercise: peak systolic blood pressure during exercise was related to the rise in albumin excretion (hypertensive patients, r = 0.68, P < 0.01; normotensive patients, r = 0.66, P < 0.05).
Effects of continuous infusion of atrial natriuretic peptide on the pulmonary hypertension induced by chronic hypoxia in rats
Authors: Zhao L. , Winter R. J. D. , Krausz T. , Hughes J. M. B.
Published: August 2015

1. The effects of the continuous infusion of atrial natriuretic peptide on the development of pulmonary hypertension were studied in rats exposed to chronic hypoxia.

2. Continuous intravenous infusion of two doses of synthetic rat atrial natriuretic peptide, 300 ng/h per rat (0.10 pmol/h per rat) and 800 ng/h per rat (0.28 pmol/h per rat), attenuated the development of pulmonary hypertension in rats exposed to chronic hypoxia (fractional concentration of oxygen in inspired air = 10%) for 7 days: (i) the pulmonary artery pressure (mean ± sd) in the vehicle-treated hypoxic group was 45 ± 6 mmHg compared with 28 ± 6 mmHg in the vehicle-treated normotoxic group (n = 8, P < 0.001); (ii) treatment with atrial natriuretic peptide in normoxia did not alter the pulmonary artery pressure, systemic blood pressure or heart rate; (iii) treatment with atrial natriuretic peptide in hypoxia resulted in a lower pulmonary artery pressure in the group treated with 800 ng of atrial natriuretic peptide/h per rat (38 ± 8 mmHg, P < 0.05 compared with the vehicle-treated hypoxic group) without affecting the systemic blood pressure or heart rate.

3. Chronic hypoxia resulted in an extension of vascular smooth muscle towards the periphery of the lung with the development of muscle in normally non-muscularized vessels (remodelling). Quantitative assessment of the small pulmonary vessels (external diameter 25–55 μm) showed that atrial natriuretic peptide treatment reduced pulmonary vascular remodelling in hypoxia (the percentage of thick-walled vessels in the peripheral lung hypoxic vehicle-treated group was 25 ± 6 compared with 19 ± 4 in the group given 300 ng of atrial natriuretic peptide/h per rat and 17 ± 7 in the group given 800 ng of atrial natriuretic peptide/h per rat, means ± sd, both P < 0.01 compared with the vehicle-treated normoxic group).

4. These data show that infusion of synthetic atrial natriuretic peptide attenuated the pulmonary vascular remodelling and associated pulmonary hypertension produced by chronic hypoxia.
Peripheral triacylglycerol extraction in the fasting and post-prandial states
Authors: Potts Jennifer L. , Fisher Rachel M. , Humphreys Sandy M. , Coppack Simon W. , Gibbons Geoffrey F. , Frayn Keith N.
Published: August 2015

1. Triacylglycerol extraction by subcutaneous adipose tissue and forearm muscle was studied in nine normal subjects after an overnight fast and after the consumption of a mixed meal.

2. There was an inverse correlation between the total plasma fractional triacylglycerol extraction across the adipose tissue and the fasting arterial plasma triacylglycerol concentration. In contrast, there was no correlation between the lower fractional triacylglycerol extraction across the forearm muscle and the fasting plasma triacylglycerol concentration.

3. Chylomicron-triacylglycerol concentrations in arterial(ized) plasma increased post-prandially and peaked at 240–300 min. There was a comparable increase in the very-low-density lipoprotein-triacylglycerol concentration, peaking at 300 min.

4. Clearance of chylomicron-triacylglycerol by adipose tissue increased after the meal (P <0.05). In contrast, the clearance of very-low-density lipoprotein-triacylglycerol by adipose tissue decreased post-prandially (P <0.05).

5. Although there was significant uptake of chylomicron-triacylglycerol by the forearm muscle post-prandially, this was less than by the adipose tissue. Very-low-density lipoprotein-triacylglycerol was unaffected by passage through the forearm muscle at any time.

6. We conclude that the extraction of lipoprotein-triacylglycerol by human adipose tissue is important in determining the fasting plasma triacylglycerol concentration. Chylomicron-triacylglycerol, appearing in the plasma post-prandially, may compete with very-low-density lipoprotein-triacylglycerol for clearance by adipose tissue lipoprotein lipase, and this mechanism may explain, at least in part, the post-prandial rise in very-low-density lipoprotein-triacylglycerol. Forearm muscle, in contrast, appears to play a much smaller role in the extraction of plasma triacylglycerol, especially that in the very-low-density lipoprotein fraction.
Sternomastoid muscle twitch maximum relaxation rate: prolonged slowing with fatigue and post-tetanic acceleration
Authors: Mak V. H. F. , Chapman F. , James C. , Spiro S. G.
Published: August 2015

1. The maximum rate of relaxation of stimulated twitches (twitch maximum relaxation rate) of the sternomastoid muscle was compared with its frequency-force curve (expressed as the ratio of force produced at a stimulation frequency of 20 Hz to that produced at 50 Hz, the 20:50 ratio) before and after fatiguing exercise of the sternomastoid muscle in 10 normal subjects. The mean (±) fresh state twitch maximum relaxation rate was 9.51 (± 0.64)% force loss/10 ms and the mean (± sem) 20:50 ratio was 73.4 (± 2.6)%.

2. The mean twitch maximum relaxation rate fell to 71.5 (± 2.2)% of the pre-fatigue value at 2 min after exercise, recovering to 73.1 (± 1.6)% by 5 min, 78.4 (± 2.34)% by 10 min and 80.6 (± 2.70)% by 60 min. The 20:50 ratio fell to 72.3 (± 3.56)% of pre-fatigue levels at 10 min after exercise and recovered to 78.8 (± 3.16)% by 60 min. There was no significant difference in the percentage falls between the two techniques.

3. Further studies were performed to determine the response of the twitch maximum relaxation rate to a prior brief tetanic stimulus or a brief maximal voluntary contraction of the muscle. Both tetanic stimulation and maximal voluntary contraction accelerated the twitch maximum relaxation rate to over 140% of the fresh state value. Both manoeuvres temporarily returned the slowed twitch maximum relaxation rate after fatiguing exercise back to the fresh state value.

4. The effect of fatiguing exercise on the time course of recovery of quadriceps twitch maximum relaxation rate was also studied in two subjects. The twitch maximum relaxation rate had not recovered to fresh state levels by 5 min after exercise in both subjects. At 10 min, one subject had recovered to the fresh state value, but the other had recovered to only 85% of the fresh state value. Both recovered to fresh state values by 1 h.

5. We conclude that the twitch maximum relaxation rate of the sternomastoid as measured from a twitch contraction has a prolonged time course of recovery after fatiguing exercise, and may follow the same time course of recovery as low-frequency fatigue. Tetanic stimulation and voluntary contractions may temporarily accelerate the relaxation rate, and therefore a distinction should be made between relaxation rates measured after a twitch contraction (twitch maximum relaxation rate) and those after tetanic stimulation or a maximum voluntary contraction (maximum relaxation rate).
Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects
Authors: Ceriello Antonio , Giugliano Dario , Quatraro Antonio , Lefebvre Pierre J.
Published: August 2015

1. In this study an acute anti-hypertensive effect of three anti-oxidant agents (vitamin C, thiopronine and glutathione) in hypertensive subjects and in both hypertensive and non-hypertensive diabetic patients is reported.

2. The anti-oxidants had no effect on blood pressure in healthy normal subjects at a dose of 6 mmol, but thiopronine and glutathione produced a significant hypotensive effect at a dose of 12 mmol.

3. These data suggest that anti-oxidants might have a dilatatory effect and that an imbalance of the nitric oxide-free radical interaction might facilitate the development of hypertension in humans.
Reduced oxygen consumption induced by vasopressin in dogs depends on systemic administration
Authors: Liard Jean-Francois
Published: August 2015

1. Arginine vasopressin reduces whole-body oxygen consumption in conscious dogs. To determine whether this decrease could result from limited oxygen delivery, studies were performed in two groups of chronically instrumented dogs.

2. In the first group (n = 7), vasopressin was infused at a rate of 18.5 pmol min−1 kg−1 while the animals were breathing 10% oxygen. Hypoxaemia alone (arterial partial pressure of oxygen 4.67 kPa) decreased whole-body oxygen delivery by 30%. The fall in whole-body oxygen consumption induced by vasopressin during hypoxaemia was not different from that measured under normoxic conditions, even though whole-body oxygen delivery was more reduced.

3. In a second group of seven dogs, hindquarter blood flow (electromagnetic flowmeter on lower abdominal aorta) and oxygen consumption (blood flow multiplied by arteriovenous oxygen difference) were measured as infusions of vasopressin were given either systemically or into the lower abdominal aorta. Systemic vasopressin infusions at 0.92, 4.6 and 18.5 pmol min−1 kg−1 reduced hindquarter blood flow, oxygen delivery and oxygen consumption, but the decreases in blood flow and oxygen delivery were dose-related whereas that in oxygen consumption was not. Intra-arterial infusions of vasopressin that increased venous concentrations as much as or more than systemic infusion of 0.92 pmol of vasopressin min−1 kg−1 had no effect on oxygen consumption, even though the higher intra-arterial rate reduced blood flow and oxygen delivery as much as the systemic infusion. Thus systemic but not locally administered vasopressin reduced hindquarter oxygen consumption.

4. Small to moderate mechanically induced reductions in hindquarter blood flow resulted in a smaller decrease in oxygen consumption than equivalent blood flow reductions induced by vasopressin. On the contrary, large mechanically induced flow reductions resulted in a larger decrease in oxygen consumption than those induced by vasopressin.

5. These results suggest that the decrease in hindquarter oxygen consumption induced by systemic vasopressin administration cannot be primarily a consequence of oxygen delivery limitation.
Plasma and platelet free catecholamine concentrations in patients with familial hypercholesterolaemia
Authors: Smith C. C. T. , Prichard B. N. C. , Betteridge D. J.
Published: August 2015

1. Plasma and platelet free catecholamine concentrations were measured in 22 normal subjects and in 10 treated and 11 untreated patients with heterozygous familial hypercholesterolaemia.

2. Plasma noradrenaline concentrations were significantly higher in both treated and untreated hypercholesterolaemic patients than in normal subjects. Adrenaline concentrations did not differ.

3. Platelet noradrenaline levels were higher in untreated hypercholesterolaemic patients than in normal subjects.

4. Positive correlations between the plasma noradrenaline concentration and the platelet noradrenaline concentration were observed in both normal subjects and hypercholesterolaemic patients.

5. Combining the data for normal subjects and hypercholesterolaemic patients revealed that the plasma noradrenaline concentration correlated positively with the plasma cholesterol concentration. The platelet noradrenaline concentration was also found to correlate with the plasma cholesterol concentration.

6. Our results suggest that an increased plasma cholesterol concentration may be associated with increased sympathetic nervous system activity as indicated by elevated plasma and platelet noradrenaline levels. Increases in circulating catecholamines may contribute to the platelet hyperaggregability seen in familial hypercholesterolaemia.
Coronary haemodynamic effects of angiotensin II in mild essential hypertension in man
Authors: Magrini Fabio , Reggiani Paolo , Ciulla Michele , Meazza Roberto , Fratianni Gerardina
Published: August 2015

1. The present investigation was carried out to elucidate the possible role of the renin-angiotensin system in modulating coronary vasomotor responses in eight patients with uncomplicated mild essential hypertension with no electrocardiographic-echocardiographic evidence of left ventricular hypertrophy.

2. Systemic and coronary haemodynamics were monitored at baseline and during intravenous infusion of angiotensin II at a subpressor dose (3 ng min−1 kg−1 for 15 min) and at a pressor dose (13 ng min−1 kg−1 for 15 min) both at rest and during handgrip exercise. Infusion of the subpressor dose of angiotensin II decreased coronary sinus blood flow at rest (207 ± 10 versus 182 ± 9 ml/min, P < 0.05) without a significant change in mean arterial pressure, heart rate or mean right atrial pressure. The performance of handgrip at baseline and during infusion of the subpressor dose of angiotensin II resulted in 55% (321 ± 13 versus 207 ± 10 ml/min) and 44% (263 ± 16 versus 182 ± 9 ml/min) increases in coronary sinus blood flow, respectively, in response to comparable increments in the rate-pressure product. At rest, infusion of the pressor dose of angiotensin II increased both coronary sinus blood flow (235 ± 11 versus 207 ± 10 ml/min, P<0.01) and the rate-pressure product (134 ± 5 versus 111 ± 8 mmHg beats/min, P<0.01). The increase in coronary sinus blood flow during isometric exercise was less than control (309 ± 18 versus 321 ± 13 ml/min, P<0.01).

3. It is thus concluded that (1) the opposite effects of angiotensin II on coronary blood flow are dose-dependent, and that (2) angiotensin II competes with the ability of the coronary arteries to dilate during handgrip exercise.
Role of renal arterial pressure in the regulation of extracellular volume in conscious dogs
Authors: Kaczmarczyk Gabriele , Schröder Klaus , Lampe Dirk , Mohnhaupt Rainer
Published: August 2015

1. This study in conscious dogs examined the quantitative effects of a reduction in the renal arterial pressure on the renal homoeostatic responses to an acute extracellular fluid volume expansion.

2. Seven female beagle dogs were chronically instrumented with two aortic catheters, one central venous catheter and a suprarenal aortic cuff, and were kept under standardized conditions on a constant high dietary sodium intake (14.5 mmol of Na+ day−1 kg−1 body weight).

3. After a 60 min control period, 0.9% (w/v) NaCl was infused at a rate of 1 ml min−1 kg−1 body weight for 60 min (infusion period). Two different protocols were applied during the infusion period: renal arterial pressure was maintained at 102 ± 1 mmHg by means of a servo-feedback control circuit (RAP-sc, 14 experiments) or was left free (RAP-f, 14 experiments).

4. During the infusion period, in the RAP-sc protocol as well as in the RAP-f protocol, the mean arterial pressure increased by 10 mmHg, the heart rate increased by 20 beats/min, the central venous pressure increased by 4 cmH2O and the glomerular filtration rate (control 5.1 ± 0.3 ml min−1 kg−1 body weight, mean ± sem) increased by 1 ml min−1 kg−1.

5. Plasma renin activity [control 0.85 ± 0.15 (RAP-f) and 1.08 ± 0.23 (RAP-sc) pmol of angiotensin I h−1 ml−1] decreased similarly in both protocols.

6. Renal sodium excretion, fractional sodium excretion and urine volume increased more in the RAP-f experiments than in the RAP-sc experiments (P<0.05), renal sodium excretion from 8.2 to 70.1 (RAP-f) and from 7.7 to 47.4 (RAP-sc) μmol min−1 kg−1 body weight, fractional sodium excretion from 1.1 to 8.0 (RAP-f) and from 1.0 to 5.4 (RAP-sc)% and urine volume from 39 to 586 (RAP-f) and from 38 to 471 (RAP-sc) μl min−1 kg−1 body weight.

7. In the RAP-f experiments as well as in the RAP-sc experiments, urinary sodium excretion increased with expansion of the extracellular fluid volume, which increased by a maximum of 21% (fasting extracellular fluid volume: 206 ± 4 ml/kg body weight, six dogs, 28 days).

8. The increase in renal arterial pressure contributed significantly to the renal homoeostatic response, as 21% less urine and 31% less sodium were excreted when the extracellular fluid volume was expanded and the renal arterial pressure was kept constant below control pressure rather than being allowed to rise. The differences in sodium and water excretion were mainly due to the effect of renal arterial pressure on tubular reabsorption. However, the striking increase in sodium and urine excretion which occurred despite the reduction in renal arterial pressure emphasizes the importance of other homoeostatic factors involved in body fluid regulation.
Exposure of rat colonic mucosa to human semen in vivo induces mucosal cytolysis, abolishes fluid absorption and raises paracellular permeability
Authors: Mendizabal M. V. , Naftalin R. J.
Published: August 2015

1. The effects of human semen on rat descending colon fluid absorption, permeability to 3H-labelled polyethylene glycol 4000 and the histological appearance of the mucosa were examined. Also, the semen was fractioned by centrifugation into plasma and sperm fractions and the effects of these fractions on rat colonic function were examined. The effects of trypsin and bacterial collagenase, mimetics of acrosin and seminal collagenase activity, were examined in order to investigate which component of human semen alters colonic permeability.

2. Contact between human semen and rat descending colonic mucosa for 3 h decreased fluid absorption from 52.0 ± 2.9 μl h−1 cm−2 (control) to 10.7 ± 3.4 μl h−1 cm−2 (P >0.001), increased the permeability to polyethylene glycol 4000 from 0.099 ± 0.006 cm/h (control) to 0.31 ± 0.04 cm/h (P>0.001) and caused cytolysis of the surface mucosa.

3. Spermatazoa inside the colonic lumen were destroyed within 1 h with release of acrosomal contents; this raised the activity of the acrosomal proteolytic enzyme acrosin by 40-fold (P >0.005) and of seminal plasma metalloproteinase (collagenase) by about twofold (mean activity 1623 ± 240 units/ml of luminal fluid).

4. The changes in colonic permeability induced by seminal plasma were similar to those induced by similar activities of clostridial collagenase.

5. We conclude that seminal collagenase is present in sufficient amounts to cause acute damage to the colonic mucosa, and that this could be a factor in facilitating viral transmission across the colonic wall.
A novel mucin sulphatase from human faeces: its identification, purification and characterization
Authors: Tsai H. H. , Sunderland D. , Gibson G. R. , Hart C. A. , Rhodes J. M.
Published: August 2015

1. Colonic mucus is heavily sulphated and it is likely that this contributes considerably to its resistance to degradation by bacterial enzymes. The presence of a mucin-desulphating enzyme in faeces could therefore be very important in determining the rate of degradation of secreted mucus and hence the level of protection of the mucosa.

2. A novel assay for mucin sulphatase has been developed using biologically labelled human colonic [35S]sulphomucin as a substrate and a mucin sulphatase has been purified from faeces by sequential high-performance gel filtration and ion-exchange chromatography.

3. The mucin sulphatase has been shown to have a pH optimum of 4.5 and activity over the pH range 3–7. It has a pI of 4.0 and is inhibited by inorganic sulphate and phosphate. The purified enzyme preparation gave a single band on electrophoresis with a molecular mass of 15000 Da. It has a Km of 41.9 mmol/l and a Vmax. of 1.17 katal/ kg for glucose 6-sulphate. The enzyme was also shown to enhance fivefold the deglycosylation of [3H]glucosamine-labelled mucin by a faecal mucin glycosidase preparation.

4. Two bacteroides spp. isolated from normal human faeces, Bacteroides fragilis and B. thetaiotaomicron, were found to be producers of mucin-desulphating enzymes.

5. Mucin sulphatase is likely to be critical in determining the rate of enzymic degradation of secreted colonic mucin.
Proton efflux from rat skeletal muscle in vivo: changes in hypertension
Authors: Kemp G. J. , Thompson C. H. , Radda G. K.
Published: August 2015

1. An analysis of the recovery kinetics of intracellular pH and phosphocreatine concentration after exercise in skeletal muscle was developed to calculate the rate of proton efflux in vivo.

2. Recovery of rat leg muscle pH after sciatic nerve stimulation was faster in spontaneously hypertensive rats than in Wistar-Kyoto controls (both n = 5).

3. Analysis of these data showed that the rate of proton efflux depends on intracellular pH, being greater at lower pH.

4. The early rate of proton efflux was greater in spontaneously hypertensive rats [measured over the first 0.8 min, 12.5 mmol min−1 kg−1 (sem 1.8) in spontaneously hypertensive rats compared with 7.6 mmol min−1 kg−1 (sem 0.4) in Wistar-Kyoto rats, P < 0.05], even though pH at the start of recovery was higher [6.30 (sem 0.03) in spontaneously hypertensive rats compared with 6.17 (sem 0.01) in Wistar-Kyoto rats, P < 0.01].

5. This novel analysis provides a quantitative estimate of the rate of proton efflux in vivo, and demonstrates directly that this is increased in spontaneously hypertensive rats, as has previously been inferred from pH changes during exercise and studies of cultured muscle cells in vitro.
An objective test for the diagnosis and grading of vasospasm in patients with Raynaud's syndrome
Authors: Allen Judith A. , Devlin Mark A. , McGrann Sean , Doherty Ciaran C.
Published: August 2015

1. Reliable objective tests for the diagnosis and grading of vasospasm would be helpful in the assessment of patients with Raynaud's syndrome.

2. Measurements of finger blood flow at local finger temperatures from 32°C down to 20°C did not reliably distinguish between patients with Raynaud's syndrome and matched control subjects.

3. Using laser Doppler flowmetry to detect blood cell flux in fingertip skin, there was no significant difference (Wilcoxon's signed rank test) in the finger systolic blood pressure of 28 patients with Raynaud's syndrome and their matched controls when the fingers were warm at 32°C.

4. Absence of flux was considered to indicate complete vasospasm and the degree of cooling required to abolish flux indicated the severity of the vasospastic condition in an individual patient.

5. Finger cooling for 5 min did not significantly alter finger systolic blood pressure in the control subjects, but abolished blood cell flux in the fingertip skin of 27 of the 28 patients with Raynaud's syndrome.

6. A grading scale was derived from the flux measurements. There was a significant correlation (r=0.75, P < 0.001) between the grading of disease severity as judged by the flux test and the clinical grade as assessed before the laboratory visit.

7. There was one false-negative result in the 28 patients with Raynaud's syndrome tested and no false-positive results in 28 matched control subjects.

8. This type of testing may prove helpful in the diagnosis and grading of vasospastic disorders.
Increases in NO2−/NO3− excretion in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure
Authors: SUZUKI Hiromichi , IKENAGA Hideki , HISHIKAWA Keiichi , NAKAKI Toshio , KATO Ryuichi , SARUTA Takao
Published: August 2015

1. Under hormonally constant conditions, the effects of a sudden increase in blood pressure on the release of endothelium-derived relaxing factor were evaluated by measuring urinary excretion of NO2−/NO3− in rats with renal denervation.

2. Elevation of blood pressure from 136 ± 2 to 153 ± 3 mmHg by an aortic clamp below the renal arteries induced a significant increase in urinary excretion of NO2−/NO3− from 76.6 ± 4.2 × 102 to 108.1 ± 8.3 × 102 pmol min−1 g−1 kidney weight (P < 0.05).

3. Infusion of NG−monomethyl-L-arginine (1 mg min−1 kg−1) without an aortic clamp raised mean blood pressure to a similar level; however, urinary excretion of NO2−/ NO3− was decreased significantly.

4. During infusion of NG−monomethyl-L-arginine, aortic occlusion caused a significant increase in blood pressure without any changes in NO2−/NO3− excretion in the urine.

5. These results suggest that the formation of NO, an indicator of endothelium-derived relaxing factor release, was increased by mechanical pressure elevation without apparent changes in hormonal and neural factors.
Effect of simvastatin on plasma lipid and lipoprotein concentrations and low-density lipoprotein metabolism in the nephrotic syndrome
Authors: Warwick G. L. , Packard C. J. , Murray L. , Grierson D. , Stewart J. P. , Shepherd J. , Boulton-Jones J. M.
Published: August 2015

1. The effect of inhibiting the rate-limiting enzyme (3-hydroxy-3-methylglutaryl-CoA reductase, EC 1.1.1.88) in cholesterol synthesis on plasma lipid and lipoprotein concentrations was investigated in 16 patients with primary glomerular disease, heavy proteinuria, well-preserved renal function and hypercholesterolaemia.

2. Detailed studies of low-density lipoprotein metabolism were performed on eight patients before and after 12 weeks of simvastatin therapy. Radioiodinated tracers were used to quantify the fractional catabolic rate of low-density lipoprotein by apolipoprotein B/E receptors and alternative pathways.

3. Simvastatin produced consistent reductions in total plasma cholesterol concentration (median 36.9%), plasma low-density lipoprotein-cholesterol concentration (43.6%) and apolipoprotein B pool size (29.9%).

4. In contrast, the changes in kinetic parameters of low-density lipoprotein metabolism showed no clear pattern. Although an increase in the receptor-mediated catabolism of low-density lipoprotein was demonstrated in five patients, no change or a slight decrease was seen in three patients. Production rates were not significantly altered, although there was a slight decrease in the median value (from 12.4 to 9.7 mg day−1 kg−1). Plasma lathosterol concentration was reduced in all eight patients (range 34–71%), indirectly confirming significant inhibition of cholesterol synthesis.

5. These results suggest that, as in patients with primary moderate hyperlipidaemia, the significant cholesterol-lowering effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in the nephrotic syndrome is accompanied by variable changes in lipoprotein metabolism. The reasons for this heterogeneous response are unclear. This reflects our limited understanding of the metabolic basis of nephrotic hyperlipidaemia and the relationship between hepatic sterol synthesis and plasma lipoprotein kinetics.
Cutaneous heat loss shortly after burn injury in children
Authors: Childs Charmaine , Stoner H. B. , Little R. A.
Published: August 2015

1. Total heat loss and its components have been studied in cool (20°C) and warm (30°C) environments in 30 healthy children and 21 children who had been burned (10-17% body surface area) 0.5-29 h previously.

2. In healthy naked children at 20°C, the partition of total heat loss was: radiation, 64%; convection, 32%; evaporation, 4%. On transfer to the warm, total heat loss was reduced by approximately 50%, with disproportionate reductions in the contributions from radiation and convection being offset, to some extent, by an increase in evaporative heat loss.

3. In patients during the first 5.5 h after injury, the magnitude and pattern of heat loss at 20°C and 30°C were similar to those in control subjects and were unaffected by bandaging.

4. Ten to twenty-nine hours after injury, when the patients were bandaged and body temperature and heat content were significantly higher than in control subjects, radiant and convective heat losses were increased, but as evaporative heat loss tended to be reduced; total heat loss in the warm was unchanged. However, at this time at 20°C, total heat loss was reduced compared with healthy children at the same ambient temperature.

5. The findings of unchanged or reduced total heat loss and reduced evaporative heat loss in injured patients are interpreted as inappropriate responses to an increased body temperature and heat content in children after burn injury.
Raised resting energy expenditure in Parkinson's disease and its relationship to muscle rigidity
Authors: Markus H. S. , Cox M. , Tomkins A. M.
Published: August 2015

1. Resting energy expenditure was measured, by indirect calorimetry, in 12 patients with Parkinson's disease and in eight healthy age-matched control subjects. In the patients with Parkinson's disease measurements were made in both the untreated state and after an injection of the dopamine agonist apomorphine (treated state). In each state muscle rigidity was recorded.

2. Resting energy expenditure was higher in patients with Parkinson's disease in both the treated and untreated states than in the control subjects. Of the patients with Parkinson's disease, seven showed no difference in resting energy expenditure between the two treatment states, whereas four showed markedly increased resting energy expenditure in the untreated state. The change in resting energy expenditure in the untreated state, as compared with the treated state, was significantly related to the development of muscle rigidity in the untreated state.

3. In Parkinson's disease, even in optimally treated patients, resting energy expenditure is raised and this may contribute to the weight loss seen in this disease. Severe muscle rigidity occurring during untreated periods results in a further increase in resting energy expenditure.
Influence of circulating insulin-like growth factor-I compared with that of intrarenal insulin-like growth factor-I on proximal nephron receptor density in rats
Authors: Hise Michael K. , Corteza Quintina , Klassen David K. , Sadler John H.
Published: August 2015

1. We examined the effects of dietary protein manipulations in partially nephrectomized (one and one-third nephrectomy) and normal rats to gain perspective on the relative importance of circulating versus intrarenal (collecting tubule) insulin-like growth factor-I in the control of proximal nephron receptor density. In addition, we studied the factors that influence liver insulin-like growth factor-I secretion in partially nephrectomized rats.

2. Dietary protein restriction (6% versus 40%) lowered circulating levels of insulin and insulin-like growth factor-I in both normal and partially nephrectomized rats up to 3 weeks after institution of the diets; however, growth hormone levels were little changed. Reduced renal mass stimulated intrarenal production of insulin-like growth factor I regardless of the diet.

3. Scatchard analysis revealed that the density of insulin-like growth factor-I receptors on glomerular and proximal tubule basolateral membranes increased when circulating levels of insulin-like growth factor-I were diminished, despite raised levels of intrarenal insulin-like growth factor-I, in partially nephrectomized rats.

4. Circulating insulin-like growth factor-I, rather than the tissue level, plays the dominant role in the control of proximal nephron receptor density under physiological conditions. Insulin, but not growth hormone, may play a role in liver insulin-like growth factor-I secretion in partially nephrectomized rats during dietary manipulations.
Analysis of factors limiting maximal exercise performance in cystic fibrosis
Authors: Lands Larry C. , Heigenhauser George J. F. , Jones Norman L.
Published: August 2015

1. Maximal exercise capacity in cystic fibrosis is influenced by both pulmonary and nutritional factors: lung disease by limiting maximal achievable ventilation, and malnutrition through a loss of muscle mass. The associated reduction in everyday activities may result in peripheral muscle deconditioning.

2. We studied 14 stable patients with cystic fibrosis (six males, eight females) and 14 healthy control subjects (seven males, seven females) in order to assess the influence of these factors on exercise performance. Subjects underwent anthropometry to estimate muscle mass, spirometry to assess ventilatory capacity, a 30 s sprint on an isokinetic cycle ergometer to assess maximal leg muscle performance, and progressive cycle ergometry to assess overall exercise capacity.

3. Compared with control subjects, the patients with cystic fibrosis were of similar age and height but weighed proportionately less [% ideal weight (mean ± sd): 94.3 ± 9.64 versus 109.5 ± 11.82] and showed evidence of airflow limitation [forced expiratory volume in 1.0s (FEV1.0) 72.5 ± 24.78 versus 112.6 ± 14.25% of predicted].

4. The patients with cystic fibrosis did less absolute (5.1 ± 1.89 versus 7.3 ± 1.97 kJ) but similar relative maximal (11.5 ± 3.41 versus 13.1 ± 3.55 kJ/kg lean body mass) sprint work. During progressive exercise, the group with cystic fibrosis achieved lower absolute [maximal O2 consumption (Vo2max.) 1.8 ± 0.527 versus 3.0 ± 0.655 litres/min] and relative (Vo2max./kg lean body mass: 40.5 ± 9.23 versus 53.0 ± 11.62 ml min−1kg−1) work levels.

5. Step-wise linear regression was carried out with Vo2max. as the dependent variable and lean body mass, FEV1.0 and 30 s sprint work as independent variables. Vo2max. was best accounted for by a two-factor equation with FEV1.0 and 30 s sprint work (r2 = 0.882), with FEV1.0 being relatively more important.

6. While noting the importance of lung disease as a limiting factor, these results suggest that peripheral muscle function is a more sensitive determinant of maximal performance than lean body mass. The 30 s sprint work results imply that the effects of mild malnutrition in cystic fibrosis are quantitative, affecting the size of the muscle mass but not the performance of the remaining muscle.
Ageing and the response of plasma insulin, glucose and C-peptide concentrations to intravenous glucose in postmenopausal women
Authors: Proudler Anthony J. , Felton Carl V. , Stevenson John C.
Published: August 2015

1. Eighty-six apparently healthy postmenopausal women not receiving hormone replacement therapy were given an intravenous glucose tolerance test. Plasma glucose, insulin and C-peptide concentrations were determined in fasting and post-glucose challenge samples.

2. Using a multivariate regression model, with predictor variables of chronological age, menopausal age and body mass index, neither chronological age nor menopausal age correlated with fasting or post-challenge plasma glucose or C-peptide concentrations. In contrast, menopausal age was positively associated with fasting plasma insulin concentration (P = 0.038, model r2 = 0.107), insulin area (P = 0.01, model r2 = 0.236) and incremental insulin area (P = 0.024, model r2 = 0.243). This relationship could not be explained by differences in lifestyle variables of alcohol consumption, physical activity, previous duration of oral contraceptive usage, history of cigarette smoking or body mass index.

3. Our findings suggest that loss of ovarian function is associated with hyperinsulinaemia, possibly via alterations in the clearance of circulating insulin from the plasma. The hyperinsulinaemia observed may contribute to the increased risk of cardiovascular disease seen in postmenopausal women.
Effect of acute plasma volume expansion on peripheral arteriolar tone in healthy subjects
Authors: Calver Alison , Collier Joe , Green Daniel , Vallance Patrick
Published: August 2015

1. Using venous occlusion plethysmography, we have investigated the forearm blood flow response in healthy subjects to the acute plasma volume expansion caused by a rapid intravenous infusion of saline. The contribution made to this response by nitric oxide has been investigated using local intra-arterial infusions of the nitric oxide synthase inhibitor NG-monomethyl-l-arginine.

2. The infusion of 1000 ml of saline over 25 min caused plasma volume to increase by about 7%, and resulted in a rise in forearm blood flow, with no change in arterial blood pressure. The onset of the blood flow response occurred within 10 min and blood flow remained elevated above baseline 20 mm after the end of the saline infusion.

3. Local intra-arterial infusion of NG-monomethyl-l-arginine alone caused a reduction in forearm blood flow which was maximal at the end of the infusion and gradually recovered to baseline levels over 40 min.

4. When local intra-arterial infusion of NG-monomethyl-l-arginine was followed by plasma volume expansion, the calculated effect of NG-monomethyl-l-arginine was such as to abolish the vasodilator response to saline.

5. The effect of local intra-arterial infusion of NG-monomethyl-l-arginine on forearm blood flow was greater when the drug was given after volume expansion had occurred, than when it was given before the administration of saline. However, in control experiments the vasoconstrictor response to noradrenaline was also enhanced after the administration of the volume load in comparison with the response to noradrenaline given alone.

6. These results are consistent with the possibility that increased local synthesis of nitric oxide contributes to the vasodilator response to volume expansion.
Long-term effects of a somatostatin analogue on renal haemodynamics and hypertrophy in diabetic rats
Authors: Muntzel Martin , Hannedouche Thierry , Niesor Roberte , Nöel Laure-Helène , Souberbielle Jean-Claude , Lacour Bernard , Drüeke Tilman
Published: August 2015

1. To determine whether treatment with octreotide, a somatostatin analogue, may diminish or prevent long-term diabetic renal hypertrophy and nephropathy, uninephrectomized streptozotocin-diabetic rats maintained under moderate glycaemic control (∼300 mg/dl) were treated with either placebo (n = 10 rat/group) or octreotide for 14 weeks. Uninephrectomized non-diabetic rats given either placebo or octreotide served as controls.

2. Average body weight was diminished and kidney weight, daily urinary protein excretion, glomerular filtration rate and renal plasma flow were elevated in both diabetic groups relative to controls.

3. Administration of octreotide reduced average body weight and packed cell volume in non-diabetic and diabetic rats compared with their respective controls, but did not affect glomerular hyperfiltration or the increase in urinary protein excretion.

4. Histological examination at 14 weeks disclosed unequivocal glomerular hypertrophy and mild glomerular and tubulointerstitial lesions consistent with early diabetic renal alterations in all diabetic rats, but there was no independent effect of octreotide treatment

5. Thus, long-term treatment with octreotide did not afford protection against the development of renal hypertrophy-hyperfiltration and the evolution of early diabetic nephropathy in rats.
Serum sialic acid concentration in patients with hypertriglyceridaemia showing the Frederickson's IIB phenotype
Authors: Crook M. , Tutt P.
Published: August 2015

1. Serum total sialic acid concentration, recently shown to be a cardiovascular risk factor, and also serum lipid-associated sialic acid concentration were measured in 15 patients with hypertriglyceridaemia (fasting serum triacylglycerol concentration > 2.3 mmol/l) showing a Frederickson's type IIB phenotype, 15 patients with hypercholesterolaemia showing a IIA phenotype and 15 age- and sex-matched normal control subjects.

2. Total serum sialic acid concentration was significantly raised in the hypertriglyceridaemic group (84.9 ± 21.5 versus 64.9 ± 20.8 mg/dl, P<0.03, Mann—Whitney U-test) compared with the normal control group, as was serum lipid-associated sialic acid concentration (23.0 ± 4.3 versus 12.0 ± 3.2 mg/dl, respectively, P<0.001, Mann—Whitney U-test).

3. Serum total sialic acid concentration was also significantly elevated in the hypertriglyceridaemic group as compared with the IIA phenotype hypercholesterolaemic group (84.9 ± 21.5 versus 58.4 ± 11.7 mg/dl, P<0.03, Mann—Whitney U-test), as was serum lipid-associated sialic acid concentration (23.0 ± 4.3 versus 14.9 ± 4.7 mg/dl, P<0.001, Mann—Whitney U-test).

4. We suggest that serum concentrations of both total sialic acid and lipid-associated sialic acid may be useful markers of cardiovascular risk which could, in part, be related to hypertriglyceridaemia.