bluuebunny/crossref_metadata_2025 huggingface dataset:
Resting energy expenditure in chronic cardiac failure
Authors: Riley M. , Elborn J. S. , McKane W. R. , Bell N. , Stanford C. F. , Nicholls D. P.
Published: August 2015

1. Resting energy expenditure has previously been shown to be elevated in the acute phase of heart failure, but the situation in the compensated state of chronic cardiac failure is unclear. Resting energy expenditure was assessed in 14 patients with stable chronic cardiac failure and 14 matched control subjects by using indirect calorimetry.

2. Resting energy expenditure was significantly elevated in the patients with chronic cardiac failure (112.6 ± 18.1 versus 87.1 ± 12.2 kJ day−1 kg−1 total body weight, P < 0.0002; mean ± sd) as were resting O2 consumption (3.88 ± 0.64 versus 3.00 ± 0.43 ml min−1 kg−1, P < 0.0002), ventilation (164 ± 40.3 versus 104 ± 16.2 ml min−1 kg−1, P < 0.0001) and heart rate (85.8 ± 16.9 versus 66.6 ± 6.9 beats/min, P < 0.001). Both the resting plasma concentration of noradrenaline (4.48 ± 1.52 versus 2.28 ± 0.96 nmol/l, P < 0.0001) and the serum concentration of free fatty acids (0.78 ± 0.21 versus 0.57 ± 0.27 mmol/l, P < 0.03) were greater in the patients with chronic cardiac failure. Analysis of covariance indicated that most of the difference in resting energy expenditure could be accounted for by the elevated ventilation in the patients with chronic cardiac failure. Arm muscle area, an index of wasting, was lower in the patients with chronic cardiac failure (39.1 ± 13.1 versus 50.5 ± 9.4 cm2, P < 0.02) and resting energy expenditure was found to account for some of this difference.

3. We conclude that an elevated basal metabolism occurs in chronic cardiac failure. It is associated with excess ventilation, and could be an aetiological factor in the development of cardiac cachexia.
Posturally induced microvascular constriction in patients with different stages of leg ischaemia: Effect of local skin heating
Authors: Ubbink Dirk Th. , Jacobs M. J. H. M. , Tangelder G. J. , Slaaf D. W. , Reneman R. S.
Published: August 2015

1. Skin microcirculation was investigated in 12 asymptomatic subjects and 76 patients, grouped according to their ankle-to-brachial systolic blood pressure index, in order to evaluate to what extent posturally induced microvascular constriction is dependent on the stage of leg ischaemia at different local skin temperatures.

2. Skin microcirculation was assessed in the supine and sitting position by using laser Doppler fluxmetry at unheated skin temperature and at 36°C, and transcutaneous oximetry at 37°C and 44°C.

3. Skin perfusion and oxygenation diminished with decreasing ankle-to-brachial systolic blood pressure index. In healthy control subjects, perfusion and oxygenation were reduced when changing from the supine to the sitting position, but were enhanced in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure < 30%), indicating disturbed posturally induced vasoconstriction.

4. Increasing the local skin temperature resulted in a higher perfusion and masked the posturally induced vasoconstriction in healthy subjects. In patients with severe leg ischaemia, however, perfusion was unaltered by the temperature increase, apparently because the microvessels were already maximally dilated. The induction of reactive hyperaemia produced no additional increase in perfusion or oxygenation.

5. It is concluded that posturally induced microvascular constriction in the skin is disturbed in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure index < 30%). Disturbed microvascular constriction upon dependency was also seen in healthy subjects after local skin heating. This suggests that posturally induced vasoconstriction is mainly regulated by local mechanisms.
Haemolytic effects of exercise
Authors: Weight Lindsay M. , Byrne Michael J. , Jacobs Peter
Published: August 2015

1. Exercise-induced haemolysis has been implicated in the sub-optimal iron status of endurance-trained athletes. Accordingly, erythrocyte survival studies using 51Cr were performed on male and female distance runners (n = 20) and sedentary control subjects (n = 10) in order to determine whether the rate of erythrocyte destruction was altered as a consequence of repetitive exercise training.

2. The chromium half-disappearance time of the male (25.4 ± 3.6 days, mean ± sd) but not the female (28.3 ± 4.6 days) athletes was significantly lower than that of the male (33.1 ± 4.5 days) and female (32.3 ± 2.6 days) control subjects (P < 0.01). The mean erythrocyte lifespan of the male and female distance runners (67.2 ± 22.2 and 72.4 ± 26.0 days, respectively) was significantly shorter than that of the non-exercising male and female subjects (113.4 ± 31.0 and 114.1 ± 29.0 days, respectively) (P < 0.01).

3. There was no correlation between the mean erythrocyte lifespan and the haemoglobin concentration, serum ferritin levels, body mass, weekly training distance, number of years running or daily protein intake. The mean cell volume and reticulocyte count measured in the same athletes before and after completing a standard 42 km marathon race were within the normal range, whereas the plasma haemoglobin levels were elevated (77.0 ± 50.5 mg/l) and the serum haptoglobin levels were decreased (0.89 ± 0.4 g/l) at rest, with a further significant decrease after running (0.69 ± 0.4 g/l) in the latter measurement (P < 0.05).

4. It is concluded that the demonstrated increase in erythrocyte turnover may be sufficient to precipitate an iron deficiency in endurance athletes when dietary intake or absorption does not meet the accelerated erythropoietic demands.
Vascular responsiveness and cation exchange in insulin-dependent diabetes
Authors: Halkin Amir , Benjamin Nigel , Doktor Hilary S. , Todd Sally D. , Viberti Giancarlo , Ritter James M.
Published: August 2015

1. We measured forearm blood flow during brachial artery infusions of vasoconstrictors (angiotensin II and noradrenaline) and vasodilators (sodium nitroprusside and carbachol) in 16 healthy control subjects and in 18 patients with uncomplicated insulin-dependent diabetes mellitus. Erythrocyte Na+/Li+ countertransport and platelet Na+/H+ antiport activities were also measured.

2. The mean basal forearm vascular resistance was 22% lower in diabetic patients than in control subjects. The effects of each infusion on forearm vascular resistance were similar in diabetic patients and control subjects.

3. Erythrocyte Na+/Li+ countertransport activities were similar in diabetic patients and control subjects. Platelet Na+/H+ exchange (Vmax.) was approximately 40% greater in diabetic patients than in control subjects, whereas the Km for Na+ was similar.

4. In diabetic patients, but not in control subjects, the responses to sodium nitroprusside and carbachol correlated inversely with Na+/Li+ countertransport in erythrocytes (rs = −0.76, P < 0.001, and rs = −0.66, P < 0.005, respectively), but not with Na+/H+ exchange in platelets.
Muscle composition in relation to age and sex
Authors: Forsberg A. M. , Nilsson E. , Werneman J. , Bergström J. , Hultman E.
Published: August 2015

1. A method is described enabling the determination of fat, water, electrolytes, protein, DNA, RNA and total creatine in a single sample of human muscle obtained by the percutaneous needle-biopsy technique. The amino acid content can also be analysed in the same muscle sample.

2. Fifty healthy subjects were studied: 29 between 19 and 40 years of age, 11 between 41 and 60 years of age, and 10 between 61 and 85 years of age. The two groups aged less than 60 years showed only marginal differences in muscle composition, whereas the highest age group showed increases in muscle fat content in relation to tissue weight and decreases in alkali-soluble protein content in relation to both tissue weight and tissue DNA content. Also, potassium, magnesium, total creatine and RNA contents were decreased in this age group when related to tissue DNA content. When alkali-soluble protein was used as a reference base, only magnesium content was decreased.

3. A comparison was also made between female (n = 23) and male (n = 18) subjects in the age groups below 60 years. Differences observed included a higher fat content in female muscle, and an increase in total creatine content in relation to tissue weight. The alkali-soluble protein content was lower per muscle cell in the females when calculated on the basis of DNA content.

4. The results show that in the assessment of muscle constituents, age and sex must be taken into account.
Elevated endothelial-cell-stimulating angiogenic factor activity in rodent glycolytic skeletal muscles
Authors: Cooper R. G. , Taylor C. M. , Choo J. J. , Weiss J. B.
Published: August 2015

1. Capillary density is greater in skeletal muscles comprised of predominantly oxidative (type I) fibres than in those comprised of mainly glycolytic (type II) fibres. In order to investigate further the angiogenic mechanisms involved in muscle capillarization, endothelial-cellstimulating angiogenic factor activities in various rodent skeletal muscles were compared.

2. Eleven untrained adult male Wistar rats were killed and the predominantly oxidative (type I) muscles, soleus and heart, the predominantly glycolytic (type II) muscle, extensor digitorum longus, and the mixed-fibre muscle, gastrocnemius, were removed. Each sample was separately homogenized and centrifuged and the supernatants were diafiltered to isolate the low-molecular-mass fraction containing endothelial-cell-stimulating angiogenic activity. This was assayed for its ability to activate latent collagenase and was expressed as units, where 1 unit represents the percentage activation of the enzyme h−1 (mg of protein in the supernatant)−1.

3. The results (medians and ranges) demonstrated significantly greater endothelial-cell-stimulating angiogenic factor activity in extensor digitorum longus muscle (2.14 units, 0.62–2.87 units, n = 13) than in soleus (0.82 units, 0.59–1.79 units, n = 15), gastrocnemius (0.34 units, 0.28–0.40 units, n = 4) or heart (0.43 units, 0.16–0.52 units, n = 11) (P< 0.01 for each) muscle.

4. These findings suggest that endothelial-cell-stimulating angiogenic activity in muscle is either inversely or not related to the local capillary density, which may be at or near a maximum in physiologically contracting, predominantly oxidative muscles.
Aluminium: Gastrointestinal absorption and renal excretion
Authors: Lote C. J. , Saunders H.
Published: August 2015

INTRODUCTION: SOURCES AND BIOAVAILABILITY OF ALUMINIUM

Aluminium is the most abundant metal and constitutes 8% of the earth's crust. It is a normal constituent of vegetable and animal tissues and is present in raw untreated water. In domestic tap-water supplies, aluminium may be present in high concentrations either from its presence in raw water or, more commonly, as a result of its use during the water-purification process. Aluminium in the metallic form is widely used for both industrial and domestic purposes, and a variety of aluminium salts are used in foods, fluids, cosmetics and medications.

The toxicity of aluminium in patients with renal failure is now well documented, and dialysis encephalopathy, osteomalacia and anaemia are recognized hazards in such patients if aluminium is not excluded from dialysis fluids and medications. The safe levels of aluminium in food, water, medications and infusion fluids for subjects with normal renal function are unknown, but aluminium has been implicated as causative agent in a number of dementia diseases, including Alzheimer's disease.
Plasma and tissue kallikrein–kinin systems during acute administration of frusemide in normotensive and hypertensive humans
Authors: Öhman K. Peter , Karlberg Bengt E.
Published: August 2015

1. This study aims to further elucidate the role of the tissue and plasma kallikrein-kinin systems in blood pressure, electrolyte and volume homoeostasis. Components thereof and of the renin-angiotensin-aldosterone system were measured in conjunction with frusemide administration, in normotensive subjects and in patients with primary hypertension.

2. Frusemide increased plasma pre-kallikrein, angiotensin II and aldosterone concentrations and plasma renin activity, whereas the plasma level of tissue kallikrein remained unchanged. Basal values and the induced changes were similar in both groups.

3. Frusemide increased the urine volume and the excretion of Na+, K+, Mg2+, Cl−, aldosterone, prostaglandin E2 and tissue kallikrein. These changes were similar in both groups, but the total tissue kallikrein excretion was significantly lower in the hypertensive patients. Excretion of electrolytes and hormones was also measured during three 24 h urine collection periods and did not differ between the two groups.

4. Thus, acute administration of frusemide to hypertensive patients and normal subjects increased the plasma level of pre-kallikrein, possibly indicating less activation to kallikrein and subsequently less kinin generation in the blood stream. This also suggests a role for the plasma kallikrein-kinin system in the regulation of vascular tone and blood volume. Circulating tissue kallikrein does not seem to be acutely involved.

5. Urinary excretion of kallikrein is reduced in patients with primary hypertension after the administration of frusemide, apparently without affecting the renal excretory response.
Effects of hypothyroidism on glucose and glutamine metabolism by the gut of the rat
Authors: Ardawi M. Salleh M. , Jalalah Sawsan M.
Published: August 2015

1. The metabolism of glucose and glutamine was studied in the small intestine and the colon of rats after 4–5 weeks of hypothyroidism.

2. Hypothyroidism resulted in increases in the plasma concentrations of ketone bodies (P < 0.05), cholesterol (P < 0.001) and urea (P < 0.001), but decreases in the plasma concentrations of free fatty acids (P < 0.05) and triacylglycerol (P < 0.001). These changes were associated with decreases in the plasma concentrations of total triiodothyronine, free tri-iodothyronine, total thyroxine and free thyroxine.

3. Hypothyroidism decreased both the DNA content (by 30.5%) and the protein content (by 23.6%) of intestinal mucosa, with the protein/DNA ratio remaining unchanged. The villi in the jejunum were shorter (P < 0.05) and the crypt depth was decreased by about 26.5% in hypothyroid rats.

4. Portal-drained visceral blood flow showed no marked change in response to hypothyroidism, but was accompanied by decreased rates of extraction of glucose, lactate and glutamine and release of glutamate, alanine and ammonia.

5. Enterocytes and colonocytes isolated from hypothyroid rats showed decreased rates of utilization and metabolism of glucose and glutamine.

6. The maximal activities of hexokinase (EC 2.7.1.1), 6-phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), citrate synthase (EC 4.1.3.28), oxoglutarate dehydrogenase (EC 1.2.4.2) and phosphate-dependent glutaminase (EC 3.5.1.2) were decreased in intestinal mucosal scrapings from hypothyroid rats. Similar decreases were obtained in colonic mucosal scrapings (except for citrate synthase and oxoglutarate dehydrogenase) from hypothyroid rats.

7. It is concluded that hypothyroidism decreases the rates of utilization of glucose and glutamine (both in vivo and in vitro) by the epithelial cells of the small intestine and colon. This may be caused by changes in protein turnover and/or the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells.
The pre-term guinea-pig: a model for the study of neonatal lung disease
Authors: Kelly F. J. , Town G. I. , Phillips G. J. , Holgate S. T. , Roche W. R. , Postle A. D.
Published: August 2015

1. Research into the pathogenesis of acute and chronic neonatal lung disease has been hampered by the lack of a suitable small-animal model of prematurity. We describe such a model that has been developed and validated in the guinea-pig.

2. Pre-term guinea-pigs delivered by Caesarian section at 65 days gestation (normal gestation 68 days) exhibited transient respiratory distress. The survival of pre-term animals was lower than that of term animals after exposure to 95% O2 (pre-term 42% versus term 79% at 96 h, P < 0.05).

3. Pulmonary histology in pre-term animals exposed to both 21% O2 and 95% O2 revealed evidence of acute lung injury with atelectasis, pulmonary oedema, fibrin deposition and inflammatory cell infiltration. No evidence of lung injury was observed in term animals exposed to 21% O2, whereas those exposed to 95% O2 showed a similar, but less pronounced, injury to that seen in preterm pups.

4. The protein concentration in bronchoalveolar lavage fluid was similar in pre-term and term animals exposed to 95% O2, but neutrophil numbers in bronchoalveolar lavage fluid tended to be greater in preterm pups.

5. Elastase-like activity, measured against succinyl-1-trialanine p-nitroanilide, was higher in bronchoalveolar lavage fluid from control pre-term animals compared with that from control term animals. Exposure to 95% O2 increased the elastase-like activity significantly in both groups. The majority of the elastase-like activity was EDTA-sensitive and thus is possibly due to metallo-elastase. Fractionation of bronchoalveolar lavage fluid indicated that the elastase-like activity was associated with a high-molecular-mass complex. Lipase treatment reduced the activity of this fraction and generated a new 40 kDa fraction.

6. We conclude that the pre-term guinea-pig is more susceptible than the term animal to lung injury after O2 exposure and thus represents a appropriate small-animal model in which to investigate the pathogenesis of acute and chronic lung injury in the pre-term infant.
Renal expression of intercellular adhesion molecule-1 in different forms of glomerulonephritis
Authors: Lhotta K. , Neumayer H. P. , Joannidis M. , Geissler D. , KöNig P.
Published: August 2015

1. Expression of intercellular adhesion molecule-1 was investigated in five normal kidneys and 47 renal biopsies with the use of monoclonal antibody 7F7 and immunoperoxidase staining.

2. In the normal kidney, intercellular adhesion molecule-1 was expressed on endothelial cells of glomerular and peritubular capillaries, on Bowman's capsule, on some interstitial cells and weakly in the mesangium.

3. Increased glomerular staining was detected in early cases of rapidly progressing glomerulonephritis (5/8) and in some cases of non-IgA mesangioproliferative glomerulonephritis (5/9), IgA nephropathy (3/5), Henoch-Schoenlein purpura (2/2), lupus nephritis (5/6) and focal segmental glomerulosclerosis (1/3). A decrease in intercellular adhesion molecule-1 expression was noted in advanced rapidly progressive glomerulonephritis (3/8), two cases of membraneous nephropathy, one severe mesangioproliferative glomerulonephritis biopsy, the two membranoproliferative glomerulonephritis biopsies and in sclerotic loops in focal segmental glomerulosclerosis.

4. Expression de novo on tubular epithelial cells occurred in rapidly progressive glomerulonephritis, in membranoproliferative glomerulonephritis, and to a lesser extent in some cases of membranous nephropathy, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, a severe case of mesangioproliferative glomerulonephritis and in the mixed essential cryoglobulinaemia case. In 63% of positive tubuli, intraluminal cells which expressed CD18, the common β-chain of leucocyte-function-associated antigen-1, Mac-1 and p150,95, were present.

5. Intercellular adhesion molecule-1 was also found on the majority (59%) of infiltrating mononuclear cells in all forms of glomerulonephritis.
Afferent baroreflex dysfunction and age-related orthostatic hypotension
Authors: Tonkin A. L. , Wing L. M. H. , Morris M. J. , Kapoor V.
Published: August 2015

1. To test the hypothesis that in apparently healthy elderly subjects with orthostatic hypotension there is afferent baroreflex dysfunction, cardiovascular and neurohumoral responses were measured after separate stimuli which activated baroreceptor (head-up tilt) and non-baroreceptor (cold stress, isometric exercise) afferent pathways.

2. In 15 healthy elderly control subjects blood pressure did not change with 60° head-up tilting and there was a moderate increase in heart rate, whereas in 13 subjects with age-related orthostatic hypotension head-up tilting was associated with a marked fall in blood pressure but a similar heart rate response to that in the elderly control group. In contrast, both groups of subjects had similar blood pressure and heart rate responses to cold stress and sustained isometric exercise.

3. Nine subjects with autonomic neuropathy also showed a marked hypotensive response to head-up tilt, but produced no pressor response to cold stress or isometric exercise.

4. The plasma concentrations of noradrenaline, adrenaline and neuropeptide-Y-like immunoreactivity rose and that of atrial natriuretic peptide fell after head-up tilt in the study population as a whole. There were no significant differences between groups despite the much greater blood pressure drops in the subjects with autonomic neuropathy and in those with age-associated orthostatic hypotension.

5. The aorto-iliac pulse wave velocity index was significantly higher in subjects with age-associated orthostatic hypotension compared with that in control subjects.

6. The pattern of responses to the separate stresses observed in the group with age-associated orthostatic hypotension is characteristic and different from that in the elderly control subjects and the subjects with autonomic neuropathy. It suggests that age-associated orthostatic hypotension is related predominantly to dysfunction in the afferent limb of the baroreflex arc, possibly partially caused by a splinting of arterial baroreceptors by non-compliant arterial walls.
Measurement of protein synthesis in human skeletal muscle: further investigation of the flooding technique
Authors: McNurlan M. A. , Essen P. , Heys S. D. , Buchan V. , Garlick P. J. , Wernerman J.
Published: August 2015

1. The rate of protein synthesis in quadriceps muscle of healthy subjects estimated from the incorporation of l-[1-13C]leucine given by continuous infusion was 1.1%/day. The estimate of protein synthesis from the incorporation of a flooding amount of labelled leucine was 1.8%/day (sd 0.65). The possibility that the higher rate obtained with the flooding technique arose from stimulation of protein synthesis by the large amount of leucine is unlikely.

2. The same rate of protein synthesis (1.7%/day, sd 0.3) was obtained with a flooding amount (0.05 g/kg) of a different amino acid, l-[1-13C]phenylalanine, as was obtained with leucine.

3. Incorporation of l-[1-13C]phenylalanine was not affected by simultaneous injection of leucine (1.7%/day, sd 0.7) or valine (1.6%/day, sd 0.4).

4. Protein synthesis, assessed in a completely different way from the proportion of polyribosomes isolated from the skeletal muscle, was unaltered by the injection of 0.05 g of l-leucine/kg (44.6%, sd 8.5 versus 43.8%, sd 7.7).

5. Good agreement in estimates of protein synthesis was observed in subjects in whom both legs were measured with both l-[1-13C]leucine (mean difference 0.16%/day) and l-[1-13C]phenylalanine (mean difference 0.2%/day).
Anti-aggregatory effects of physiological concentrations of adenosine in human whole blood as assessed by filtragometry
Authors: Söderbäck U. , Sollevi A. , Wallen N. H. , Larsson P. T. , Hjemdahl P.
Published: August 2015

1. The anti-aggregatory effect of adenosine (0.3–10 μmol/l), alone or in combination with the adenosine-uptake inhibitor dipyridamole (2 μmol/l), was studied in vitro in whole blood from 11 healthy subjects by filtragometry.

2. ADP (0.05–0.1 μmol/l) was used to reduce the filter occlusion time (tA, a measure of platelet aggregate formation in blood) from approximately 600 s to 71–101 s in the absence of other agents.

3. Adenosine was infused into the tubing system of the filtragometer, yielding a contact time of >25 s with the blood before the filter. Adenosine did not influence the aggregatory response to ADP significantly at 0.3 μmol/l in plasma, whereas tA was prolonged by 19 ± 6% (P <0.02) at 1 μmol/l adenosine and by 259 ± 78% (P <0.02) at 3 μmol/l adenosine.

4. When the rapid elimination of adenosine from plasma was prevented by 2 μmol/l dipyridamole, adenosine caused marked prolongation of ADP-induced tA, with significant effects at 0.3 μmol/l (± 143 ± 72%, P <0.05). Dipyridamole per se did not affect tA values.

5. The present results suggest that adenosine has a transient anti-aggregatory effect in whole blood at about 0.3 μmol/l, as this is the highest possible calculated concentration of adenosine at the filter of the apparatus when 1 μmol/l adenosine is infused in the absence of dipyridamole or when 0.3 μmol/l adenosine is infused in its presence.

6. It is concluded that adenosine has anti-aggregatory effects at submicromolar (physiological) concentrations in human whole blood. The effect of adenosine seems to be transient, indicating a role for adenosine as a localized platelet-stabilizing factor in the vicinity of, for example, the endothelium.
Serum creatine kinase MM isoforms in hypertrophic cardiomyopathy
Authors: Hamada Mareomi , Ohtani Takashi , Sekiya Michihito , Fujiwara Yasushi , Sumimoto Takumi , Hiwada Kunio , Morita Shigeki , Tsukada Hiroshi
Published: August 2015

1. To determine whether a persistent release of creatine kinase from the myocardium occurs in patients with hypertrophic cardiomyopathy, the activities of serum creatine kinase MM isoforms were measured in 22 patients with hypertrophic cardiomyopathy and in 14 normal control subjects.

2. Serum creatine kinase MB activity was significantly higher in patients with hypertrophic cardiomyopathy (7.8 ± 3.8 i.u./l) than in normal control subjects (0.4 ± 0.8 i.u./l; P < 0.01).

3. Serum MMa, MMb and MMc activities in patients with hypertrophic cardiomyopathy were 19.4 ± 4.1%, 26.7 ± 2.5% and 33.5 ± 7.0% of the total creatine kinase MM activity, respectively. These values for each isoform were significantly different from those in normal control subjects (11.3 ± 3.0%, 21.5 ± 4.4% and 40.7 ± 7.0%, respectively). The MMa/MMc activity ratio was significantly higher in patients with hypertrophic cardiomyopathy (0.61 ± 0.25) than in normal control subjects (0.30 ± 0.10; P < 0.01).

4. Our results indicate that a small amount of the myocardial tissue isoform of creatine kinase MM (MMa) is constantly released in many patients with hypertrophic cardiomyopathy.
Effect of varying alveolar oxygen partial pressure on diffusing capacity for nitric oxide and carbon monoxide, membrane diffusing capacity and lung capillary blood volume
Authors: Borland C. D. R. , Cox Y.
Published: August 2015

1. To examine the effect of varying oxygen partial pressure (Pao2) on nitric oxide (DLNO) and carbon monoxide (DLCO) diffusing capacity (transfer factor), 10 subjects performed combined DLCO/DLNO measurements with the inspired mixture made up with three different oxygen concentrations (25%, 18% and 15%) to give Pao2 values of 12–20 kPa.

2. A novel method is described for calculating membrane diffusing capacity (DM) and pulmonary capillary volume (Qc) from DLNO and DLCO.

3. The mean DMCO was 52.89 mmol min−1 kPa−1 and Qc was 0.056 litre. Reducing Pao2 from 20 to 12 kPa resulted in an increase in DLCO = −0.124 (O2%) + 11.67 (P < 0.001) and a fall in DLNO = 0.538 (O2%) + 32.01 (P < 0.001) and a fall in DLNO/DLCO = 0.107 (O2%) + 2.52 (P < 0.001). DM (P = 0.59) and Qc (P = 0.64) also tended to fall with falling Pao2.

4. It appears more likely that the minor reduction in DLNO that we have observed with falling Pao2 is due to diffusion rather than reaction limitation.
Islet amyloid polypeptide: production by an osteoblast cell line and possible role as a paracrine regulator of osteoclast function in man
Authors: Gilbey Stephen G. , Ghatei Mohammad A. , Bretherton-Watt Deborah , Zaidi Mone , Jones Phillip M. , Perera Tim , Beacham Jeremy , Girgis Samia , Bloom Stephen R.
Published: August 2015

1. The recently discovered peptide islet amyloid polypeptide shows considerable sequence homology with calcitonin-gene-related peptide, itself an alternative product of the calcitonin gene. The possibility that islet amyloid polypeptide might affect calcium homoeostasis and bone cell function was investigated.

2. Islet amyloid polypeptide messenger RNA was found to be expressed by human HTb 96 osteoblast-like cells in culture, and islet amyloid polypeptide immunoreactivity was present in the cell culture medium.

3. Infusion of islet amyloid polypeptide (150 pmol min−1 kg−1) caused a fall in serum calcium and phosphate concentrations in five patients with Paget's disease of the bone. This was similar to that caused by infusion of calcitonin (50 pmol min−1 kg−1).

4. These findings raise the possibility that islet amyloid polypeptide may act as a local factor within bone, produced by osteoblasts and regulating osteoclast function. The possibility of an action of islet amyloid polypeptide on the renal handling of calcium seems unlikely but is not totally excluded.
Renal filtration, reabsorption and excretion of aluminium in the rat
Authors: Lote C. J. , Wood J. A. , Saunders H. C.
Published: August 2015

1. Plasma and urinary aluminium levels, and renal function, were investigated in a control group of rats (n = 5) and in two groups that received an intravenous bolus dose of aluminium chloride (either 25 μg or 800 μg of aluminium, n = 7 and 5, respectively).

2. In the control group (plasma aluminium concentration 76.8 ± 14.2 ng/ml), 59.4 ± 3.5% of the plasma aluminium was ultrafilterable. The percentage ultrafilterable after the administration of 25 μg of aluminium was 41.9 ± 7.8 (plasma concentration 154.3 ± 18.6 ng/ml). However, after administration of 800 μg of aluminium, to give a plasma concentration of 19800 ± 2956 ng/ml, only 1.06 ± 0.13% was ultrafilterable.

3. Such results have generally been interpreted as indicating an increase in protein-binding of aluminium with increasing aluminium concentration. In buffered aqueous solutions of aluminium chloride at pH 7.4, with an aluminium concentration of 189 ± 6 ng/ml, 96.12 ± 0.02% was ultrafilterable (n = 6). This concentration is comparable with that attained in the low-dose (25 μg) aluminium group of animals and suggests that the difference between the ultrafilterable percentage of aluminium in plasma compared with that in aqueous solution is indeed due to the binding of aluminium to high Mr material (proteins). In contrast, however, in an aqueous buffered (pH 7.4) solution containing 28200 ng of aluminium/ml, only 1.05 ± 0.09% was ultrafilterable. This indicates insolubility (i.e. colloid formation) of the aluminium at this high concentration. The same percentage (1.06 ± 0.13) was ultrafilterable from plasma from the high-dose (800 μg) aluminium group with a plasma aluminium concentration of 19 800 ± 2956 ng/ ml. This low ultrafilterable fraction is thus attributable to the insolubility of aluminium at this concentration, rather than to protein binding.

4. The fractional excretion of aluminium in the control group was approximately 10%. It was somewhat higher in the low-dose aluminium group, and reached 53% in the high-dose aluminium group. Nevertheless, it is clear that the kidneys are inefficient at excreting aluminium, so that after aluminium administration there is a prolonged period (several hours) during which the plasma aluminium concentration remains elevated and thus tissue deposition may occur.
Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose
Authors: Pukrittayakamee S. , White N.J. , Davis T. M. E. , Looareesuwan S. , Supanaranond W. , Desakorn V. , Chaivisuth B. , Williamson D. H.
Published: August 2015

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence.

2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min−1 kg−1, mean (sd)], but this difference was not statistically significant (P= 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004).

3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min−1 kg−1] and convalescent study [12.8 (2.1) ml min−1 kg−1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)].

4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study.

5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria. Since galactose does not stimulate insulin secretion directly and does not appear to increase plasma lactate concentrations, this simple sugar may be an alternative to glucose in the treatment of malaria-associated hypoglycaemia.
Location of enkephalinase and functional effects of [Leu5] enkephalin and inhibition of enkephalinase in the feline main pancreatic and bile duct sphincters
Authors: Thune A. , Jivegård L. , Pollard H. , Moreau J. , Schwartz J. C. , Svanvik J.
Published: August 2015

1. Morphological studies have demonstrated enkephalinergic nerve fibres in proximity to the sphincter of Oddi, and opiates are known to contract this sphincter. In this study, the flow resistances in the common bile duct and main pancreatic duct sphincters were studied simultaneously in anaesthetized cats using a perfusion technique.

2. Naloxone did not affect the activity of these sphincters under basal conditions, indicating that there is no basal enkephalinergic tone.

3. The response to [Leu5]enkephalin (0.015–15 μg/kg), morphine (1 mg/kg) and ketamine (10 mg/kg) was a naloxone-sensitive increased activity in the sphincters with a raised frequency of phasic contractions. The threshold dose for an effect of [Leu5]enkephalin on the sphincter of Oddi was 0.015 μg/kg and a maximal response was observed at 0.75 μg/kg. There were no differences in the response of the main pancreatic duct sphincter and the bile duct sphincter to the different drugs.

4. Immunoautoradiographic studies demonstrated enkephalinase in the spincter of Oddi.

5. Acetorphan (3 mg/kg intravenously), which inhibits endogenous enkephalinase both in the peripheral and the central nervous system when administered parenterally, caused a naloxone-sensitive contraction, whereas thiorphan (3–20 mg/kg), an enkephalinase inhibitor that does not easily penetrate the blood-brain barrier, had no effect on the sphincter of Oddi.

6. These results show that endogenous and exogenous opiates influence the function of the feline sphincter of Oddi and that enkephalins may be involved in the physiological control of this sphincter, although not under basal conditions.
Adaptation to a diet low in protein: effect of complex carbohydrate upon urea kinetics in normal man
Authors: Langran M. , Moran B. J. , Murphy J. L. , Jackson A. A.
Published: August 2015

1. Urea kinetics were measured by using prime/intermittent oral doses of [15N15N]urea in five healthy men taking formula diets adequate in energy and containing either 70 or 35 g of protein/day. In some studies the low-protein diet was supplemented with non-starch polysaccharides in the form of ispaghula husk or ripe bananas.

2. On the 70 g of protein/day diet urea production was 132% of intake. Only 54% of the urea produced was excreted in the urine with 46% being salvaged in the colon; 90% of the salvaged nitrogen was retained in the metabolic nitrogen pool.

3. On the 35 g of protein/day diet the small decrease in urea production rate compared with that on the 70 g of protein/day diet was not significant, but only 36% of the urea produced was excreted in urine, with the majority, 64%, being salvaged.

4. The extent of urea-nitrogen salvaging on the 35 g of protein/day diet was similar in magnitude to the decrease in nitrogen intake, with the effect that the sum of intake and salvaged nitrogen did not differ between the 35 and the 70 g of protein/day diets. This implies that quantitative control is exerted over the rate at which urea nitrogen is salvaged.

5. The addition of non-starch polysaccharides to the 35 g of protein/day diet had a demonstrable effect upon faecal weight and composition, but did not exert any significant influence upon urea kinetics.

6. It is concluded that large changes in the rate of urea production are not necessary for adaptation to a low-protein diet, rather the salvaging of urea nitrogen in the lower bowel appears to be an important mechanism through which the body adapts to a low-protein diet. The salvaging of urea nitrogen by the colon makes an important contribution to the conservation of body nitrogen.
Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man
Authors: Johnson A. B. , Argyraki M. , Thow J. C. , Cooper B. G. , Fulcher G. , Taylor R.
Published: August 2015

1. Experimental elevation of plasma non-esterified fatty acid concentrations has been postulated to decrease insulin-stimulated glucose oxidation and storage rates. Possible mechanisms were examined by measuring skeletal muscle glycogen synthase activity and muscle glycogen content before and during hyperinsulinaemia while fasting plasma non-esterified fatty acid levels were maintained.

2. Fasting plasma non-esterified fatty acid levels were maintained in seven healthy male subjects by infusion of 20% (w/v) Intralipid (1 ml/min) for 120 min before and during a 240 min hyperinsulinaemic euglycaemic clamp (100 m-units h−1 kg−1) combined with indirect calorimetry. On the control day, 0.154 mol/l NaCl was infused. Vastus lateralis muscle biopsy was performed before and at the end of the insulin infusion.

3. On the Intralipid study day serum triacylglycerol (2.24 ± 0.20 versus 0.67 ± 0.10 mmol/l), plasma non-esterified fatty acid (395 ± 13 versus 51 ± 1 μmol/l), blood glycerol (152 ± 2 versus 11 ± 1 μmol/l) and blood 3-hydroxybutyrate clamp levels [mean (95% confidence interval)] [81 (64–104) versus 4 (3–5) μmol/l] were all significantly higher (all P < 0.001) than on the control study day. Lipid oxidation rates were also elevated (1.07 ± 0.07 versus 0.27 ± 0.08 mg min−1 kg−1, P < 0.001). During the clamp with Intralipid infusion, insulin-stimulated whole-body glucose disposal decreased by 28% (from 8.53 ± 0.77 to 6.17 ± 0.71 mg min−1 kg−1, P < 0.005). This was the result of a 48% decrease in glucose oxidation (3.77 ± 0.32 to 1.95 ± 0.21 mg min−1 kg−1, P<0.001), with no significant change in nonoxidative glucose disposal (4.76 ± 0.49 to 4.22 ± 0.57 mg min−1 kg−1, not significant).

4. Basal and insulin-stimulated glycogen synthase activities (13.1 ± 1.9 versus 11.4 ± 2.3% and 30.8 ± 2.3 versus 27.6 ± 4.5%, respectively) were unaffected by the increased plasma non-esterified fatty acid levels. Similarly, basal (36.1 ± 2.7 versus 37.2 ± 1.4 μmol/g) and stimulated (40.0 ± 0.6 versus 37.6 ± 4.4 μmol/g) muscle glycogen levels were unaltered. Insulin-stimulated hexokinase activity was also not affected (0.52 ± 0.08 versus 0.60 ± 0.08 units/g wet weight).

5. Maintenance of plasma non-esterified fatty acid levels at fasting values resulted in an increase in lipid oxidation and was associated with a decrease in insulin-stimulated whole-body glucose uptake and glucose oxidation rates, but no change in non-oxidative glucose disposal. Increased plasma non-esterified fatty acid levels did not appear to have a direct inhibitory effect on glycogen synthase activity or storage of glucose as glycogen at these insulin levels.
Interactions between hypoxic and almitrine-induced vasoconstriction in the rat lung
Authors: Russell P. C. , Emery C. J. , Nicholl J. , Barer G. R. , Howard P.
Published: August 2015

1. To test whether almitrine might improve the arterial partial pressure of O2 in patients with chronic obstructive airways disease by improvement of ventilation-perfusion matching, we looked at the interaction between hypoxic and almitrine-induced vasoconstriction in isolated rat lungs perfused with blood at constant flow. Increases in pressure represented increases in resistance.

2. Almitrine, given in increasing doses between challenges with 2% O2, enhanced hypoxic vasoconstriction at low doses but attenuated it at high doses.

3. Stimulus-response curves to hypoxia of increasing severity gave a sigmoid curve.

4. Almitrine solvent caused small changes in pulmonary artery pressure and shifted the stimulus-response curve slightly in a parallel fashion.

5. Small doses of almitrine enhanced the action of mild to moderate hypoxia, medium doses attenuated moderately severe hypoxia, whereas high doses depressed vasoconstriction due to all degrees of hypoxia.

6. These effects of almitrine on hypoxic vasoconstriction were compared with the effect of solvent by analysis of variance; the results substantiated significant enhancement of hypoxia by small doses and attenuation by large doses.

7. In patients, if similar effects apply, small doses of almitrine would assist ventilation-perfusion matching, but large doses might worsen it.

8. Almitrine-induced vasoconstriction was attenuated by a fall in perfusate temperature in a similar manner to hypoxic vasoconstriction. It was also attenuated by three drugs, chlorpheniramine, propanolol and diethylcarbamazine, all of which also decrease hypoxic vasoconstriction. The similarity between hypoxic and almitrine-induced pulmonary vasoconstriction is further confirmed.
Leg extensor power and functional performance in very old men and women
Authors: Bassey E. Joan , Fiatarone Maria A. , O'neill Evelyn F. , Kelly Margaret , Evans William J. , Lipsitz Lewis A.
Published: August 2015

1. Residents of a chronic care hospital (13 men of mean age 88.5 ± 6 sd years and 13 women of mean age 86.5 ± 6 sd years) who had multiple pathologies were assessed for leg extensor capability in several ways.

2. A custom-built rig was used to assess leg extensor power, that is, maximal power output over less than 1 s in a single extension of one leg. Performance measures were obtained by timing chair rises (from a standard chair 0.43 m high), stair climbing (four risers, total height 0.635 m) and a walk (6.1 m). For each measurement the best of several trials were recorded as definitive.

3. Leg extensor power was significantly correlated with all performance measures, but the performance measures were not related to each other except for chair rising and walking speed.

4. Women had significantly less extensor power than men, but their power explained more of the variance in performance, e.g. power accounted for 86% of the variance in walking speed.

5. There was no relation within the group between age and any of the variables measured.

6. Measurement of leg extensor power in frail elderly people may prove useful in focusing effective rehabilitation programmes.
Cutaneous vascular responses and thermoregulation in relation to age
Authors: Khan F. , Spence V. A. , Belch J. J. F.
Published: August 2015

1. Sympathetic vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge were assessed in fingertip skin in relation to age and were correlated with vasoconstrictor ability during body cooling. The above relationship was also examined in diabetic patients in whom vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge had been shown previously to be markedly impaired.

2. Vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge, measured by laser Doppler flowmetry, were significantly reduced in the elderly group, although individual responses varied from normal to absent, and they also had a considerably greater variability as measured on three separate occasions than seen in young subjects. Discriminant analysis showed that, from each of three occasions, 65% of vasoconstrictor responses were abnormal in the elderly group.

3. Body cooling was performed by reducing the environmental temperature from 40°C to 12°C, and the time taken for blood flow to fall to 75%, 50% and 25% of the pre-cooling level (VC75, VC50, VC25, respectively) was calculated. Vasoconstriction was rapid in young subjects and was consistent with good vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge. In the elderly group, vasoconstriction was slower, but only the VC25 value differed significantly [elderly group, 13.3(7.9–31.0) min, young group, 5.7(2.7–15.5) min; median (interquartile range); P < 0.05]. A poor vasoconstrictor response to contralateral arm cold challenge did not always correlate with an impaired response to body cooling in the elderly group, but, importantly, a diminished vasoconstrictor response to body cooling, with no spontaneous sympathetic vasoconstrictor bursts, was associated with an impaired vasoconstrictor response to contralateral arm cold challenge. Diabetic patients all had markedly reduced vasoconstrictor responses to inspiratory gasp, contralateral arm cold challenge and body cooling.

4. It is concluded that elderly subjects have diminished sympathetic vasoconstrictor responses. This may be a significant factor contributing to thermoregulatory impairment in the elderly, thereby rendering them more susceptible to the harmful effects of cold weather.