bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute metabolic and hormonal responses to the inhibition of lipolysis in non-obese patients with non-insulin-dependent (type 2) diabetes mellitus: effects of acipimox
Authors: Fulcher G. R. , Walker M. , Catalano C. , Farrer M. , Alberti K. G. M. M. 
Published: August 2015

1. Increased rates of fatty acid oxidation are frequently observed in patients with non-insulin-dependent diabetes mellitus and may contribute to hyperglycaemia by both decreasing peripheral glucose disposal and, more importantly, by increasing the rate of gluconeogenesis and therefore hepatic glucose output. Despite this relationship between lipid and carbohydrate metabolism, fasting glucose concentrations do not fall acutely in patients with non-insulin-dependent diabetes mellitus when plasma non-esterified fatty acid concentrations and lipid oxidation rates are decreased, questioning the importance of this interaction to glycaemic control. We have therefore measured the acute changes that occur 120–150 min after administration of 500 mg of the anti-lipolytic agent acipimox in eight non-obese male patients with non-insulin-dependent diabetes mellitus.
2. After administration of acipimox, lipolysis was inhibited as reflected by lower plasma non-esterified fatty acid (0.05 ± 0.02 versus 0.55 ± 0.05 mmol/1, P &lt; 0.001) and blood glycerol (8 ± 1 versus 56 ± 8 μmol/l, P &lt; 0.001) concentrations. The lipid oxidation rate was decreased (0.63 ± 0.05 versus 1.02 ± 0.08 mg min−1 kg−1, P &lt; 0.001), whereas there was a significant increase in the carbohydrate oxidation rate (1.93 ± 0.17 versus 1.22 ± 0.18 mg min−1 kg−1, P = 0.02). In addition, in the lipolysis-suppressed patients, there was a significant increase in serum cortisol (329 ± 47 versus 196 ± 43 nmol/l, P=0.03), serum growth hormone (5.44 ± 2.1 versus 0.6 ± 0.2 ng/ml, P=0.04), plasma glucagon (12 ± 2.5 versus 8.2 ± 2.0 ng min−1 ml−1, P = 0.005), plasma noradrenaline (1.82 ± 0.26 versus 1.39 ± 0.21 nmol/l, P=0.004) and adrenaline (0.32 ± 0.08 versus 0.20 ± 0.05 nmol/l, P=0.04) concentrations compared with control. Despite this marked hormonal response, there was no difference in hepatic glucose output, fasting blood glucose concentration or peripheral glucose disposal, although non-oxidative glucose disposal was less after acipimox (0.16 ± 0.16 versus 0.74 ± 0.20 mg min−1 kg−1, P=0.05).
3. We conclude that an acute decrease in fatty acid oxidation results in a switch to oxidation of glucose at the expense of glycogen stores, but apparently does not increase peripheral glucose uptake. Hepatic glucose output and fasting blood glucose concentration are maintained by an acute counter-regulatory response which presumably increases glycogen breakdown. Inhibitors of lipolysis and lipid oxidation are therefore more likely to lower fasting blood glucose concentration in the glycogen-depleted state.
Pernicious anaemia as a risk factor for osteoporosis
Authors: Eastell Richard , Vieira Nancy E. , Yergey Alfred L. , Wahner Heinz W. , Silverstein Murray N. , Kumar Rajiv , RIGGS B. Lawrence 
Published: August 2015

1. If gastric acid is necessary for the absorption of dietary calcium, the total absence of gastric acid secretion that occurs in pernicious anaemia could result in bone loss. To investigate this, we measured calcium absorption and bone density in 21 postmenopausal women (ages 51–76 years) with pernicious anaemia and in 24 normal postmenopausal women (ages 51–79 years).
2. Relative to the normal women, in the women with pernicious anaemia the bone mineral density of the lumbar spine was decreased by 16% (P &lt; 0.001).
3. After adjustment for age and body weight, lumbar spine bone mineral density correlated with the serum concentration of group 1 pepsinogens (a group of proteins produced by the gastric fundus) (r= 0.61, P &lt; 0.01).
4. Despite achlorhydria, the women with pernicious anaemia had normal true fractional calcium absorption and normal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D.
5. We conclude that gastric acid is not required for the absorption of dietary calcium. Thus, the loss of cancellous bone must be caused by some mechanism yet to be identified.
Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2 production
Authors: Calder Philip C. , Newsholme Eric A. 
Published: August 2015

1. The effects of a variety of fatty acids on human peripheral blood lymphocyte proliferation stimulated by concanavalin A or purified protein derivative of Mycobacterium tuberculosis were studied.
2. The proliferative response to concanavalin A was inhibited by all of the polyunsaturated fatty acids tested (eicosapentaenoate, arachidonate, docosahexaenoate, linoleate and α-linolenate) and also by the saturated fatty acid, stearate. The greatest inhibition of proliferation (approximately 85%) was caused by eicosapentaenoate.
3. The proliferative response to the purified protein derivative of Mycobacterium tuberculosis was inhibited by all of the polyunsaturated fatty acids tested, except α-linolenate, and also by stearate. The greatest inhibition of proliferation (approximately 75%) was caused by eicosapentaenoate.
4. The pattern of inhibition of proliferation by fatty acids was similar to that previously reported for rat lymphocytes with one exception: oleate did not inhibit human lymphocyte proliferation.
5. The proliferation of T-lymphocytes is dependent upon their ability to synthesize and secrete the cytokine, interleukin-2. In the presence of mitogen the concentration of interleukin-2 in the culture medium increased markedly above that in the medium of non-stimulated cells.
6. All polyunsaturated fatty acids tested caused a decrease in the concentration of interleukin-2; the greatest decrease (approximately 90%) was caused by eicosapentaenoate.
7. There was a good correlation between lymphocyte proliferation in the presence of fatty acids and interleukin-2 concentration. However, stearate did not decrease the interleukin-2 concentration but did inhibit lymphocyte proliferation.
8. These observations suggest that, although fatty acid suppression of interleukin-2 production may play a role in the inhibition of proliferation, it is not the sole mechanism by which fatty acids act.
Systemic and splanchnic haemodynamic effects of pentifylline in rats with portal hypertension
Authors: Dagenais M. , Pomier-Layrargues G. , Rocheleau B. , Giroux L. , Huet P.-M. 
Published: August 2015

1. The systemic and splanchnic haemodynamic effects of pentifylline (40 mg/kg body weight intravenously) were assessed in rats with portal hypertension associated either with CCl4-induced cirrhosis (n= 13) or portal vein ligation (n=13).
2. Heparinized catheters were placed into the portal vein, inferior vena cava, aorta and left ventricle with exits from the neck. Haemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabelled microspheres and the reference sample method in seven rats in each group; portal-systemic shunting was measured using microsphere injection in the ileo-colic vein in six rats in each group.
3. Forty-five minutes after injection, pentifylline had no effect on mean arterial pressure, cardiac output, peripheral resistance, portal venous flow, hepatic artery flow or portal-systemic shunting in either group of rats with portal hypertension. The drug lowered portal pressure (−18%) in cirrhotic rats, but not in portal-vein-ligated rats.
4. These data demonstrate that pentifylline lowers portal pressure in cirrhotic rats without affecting portal venous flow and portal-systemic shunting; this effect is possibly mediated by changes in intrahepatic resistance related to the effects of pentifylline on blood viscosity and/or on intrahepatic vasomotor tone.
Differential responses in superior mesenteric artery blood flow may explain the variant pressor responses to clonidine in two groups with sympathetic denervation
Authors: Thomaides T. N. , Chaudhuri K. Ray , Maule S. , Mathias C. J. 
Published: August 2015

1. Measurement of superior mesenteric artery blood flow along with systemic and regional haemodynamic changes in blood pressure, heart rate, cardiac index, forearm blood flow, digital skin blood flow and index finger temperature were made before and after administration of clonidine (2 μg/kg body weight intravenously) in 10 patients with multiple-system atrophy, 10 patients with pure autonomic failure and 15 age-matched healthy control subjects.
2. After clonidine, blood pressure fell in patients with multiple-system atrophy and control subjects but not in patients with pure autonomic failure.
3. Resting superior mesenteric artery blood flow was similar in patients with multiple-system atrophy and control subjects, but was higher in patients with pure autonomic failure. The fall in blood pressure after clonidine was accompanied by active dilatation of the superior mesenteric artery in patients with multiple-system atrophy and control subjects. This did not occur in patients with pure autonomic failure.
4. After clonidine, there was a fall in cardiac index in patients with multiple-system atrophy.
5. After clonidine, changes in other haemodynamic parameters were not significant in any group, except for a fall in forearm blood flow and a rise in index finger temperature in control subjects.
6. We conclude that after clonidine there are differential superior mesenteric artery blood flow responses in the two groups with autonomic failure (multiple-system atrophy and pure autonomic failure). These may relate to differences in the site of the sympathetic lesion, which is considered to be mainly central in multiple-system atrophy but peripheral in pure autonomic failure. The blood pressure responses to clonidine in the two groups may be largely dependent on changes in superior mesenteric artery blood flow.
Increased urinary excretion of prostaglandin E2 in patients with idiopathic hypercalciuria is a primary phenomenon
Authors: Henríquez-la Roche C. , Rodríguez-Iturbe B. , Parra G. 
Published: August 2015

1. Urinary excretion of prostaglandin E2 is increased in patients with idiopathic hypercalciuria, but in order to conclude that hyperprostaglandinuria is a primary phenomenon, it must be demonstrated that high levels of urinary prostaglandin E2 can be dissociated from other factors, such as urine volume and natriuresis, and from the hypercalciuria itself.
2. We studied 10 patients with idiopathic hypercalciuria and 10 control subjects on high and low calcium diets providing daily calcium intakes of 30-35 mmol and 7.5-10 mmol, respectively, and similar sodium intakes. In addition, patients with idiopathic hypercalciuria and control subjects were studied during water restriction and water diuresis.
3. Urinary prostaglandin E2 excretion was more than twice as high in patients with idiopathic hypercalciuria than in control subjects on the low and high calcium diets as well as during water restriction and water diuresis (P&lt;0.01).
4. Urinary prostaglandin E2 excretion was not affected by changes in urinary calcium excretion in patients with idiopathic hypercalciuria and in control subjects. Patients with idiopathic hypercalciuria on the low calcium diet and control subjects on the high calcium diet had similar levels of calciuria and natriuresis, yet urinary prostaglandin E2 excretion (mean ± SEM) was 11.62 ± 1.71 nmol/day in the patients with idiopathic hypercalciuria and 3.26 ± 0.48 nmol/day in the control subjects (P= 0.0006).
5. These results indicate that increased urinary prostaglandin E2 excretion is a cardinal characteristic of patients with idiopathic hypercalciuria.
Basal metabolic rate in adults with growth hormone deficiency and in patients with acromegaly: relationship with lean body mass, plasma insulin level and leucocyte sodium pump activity
Authors: Salomon Franco , Cuneo Ross C. , Hesp Richard , Morris Jenny F. , Poston Lucilla , Sönksen Peter H. 
Published: August 2015

1. The relationship of lean body mass, plasma insulin concentration and leucocyte active sodium transport with basal metabolic rate was investigated in 24 adults with growth hormone deficiency before and after treatment with recombinant human growth hormone and in 10 patients with untreated acromegaly.
2. Based on total-body potassium determined by whole-body 40K counting, patients with acromegaly had increased lean body mass, whereas lack of growth hormone was associated with decreased lean body mass.
3. By indirect calorimetry, patients with acromegaly had increased basal metabolic rates and patients with growth hormone deficiency had decreased values when expressed as percentages of values predicted from the WHO/FAO/UNU equations. Basal metabolic rate expressed in terms of lean body mass was similar in acromegaly and growth hormone deficiency, but was higher than normal in both patient groups.
4. The leucocyte ouabain-sensitive sodium efflux rate constant was decreased in both patients with acromegaly and patients with growth hormone deficiency, and there was no correlation with basal energy expenditure, fasting plasma insulin level or serum growth hormone level.
5. There was no increase in the sodium efflux rate constant in patients with growth hormone deficiency after 1 month on treatment with recombinant human growth hormone.
6. Apparent differences in basal metabolic rate in growth hormone deficiency and acromegaly are due to changes in lean body mass. Both adults with growth hormone deficiency and patients with acromegaly have increased energy expenditure, probably owing to changes in fuel metabolism which are not reflected in the leucocyte sodium pump activity.
Role of kinins in pain and hyperalgesia: psychophysical studies in a patient with kininogen deficiency
Authors: Raja Srinivasa N. , Campbell James N. , Meyer Richard A. , Colman Robert W. 
Published: August 2015

1. Bradykinin is considered to be an important mediator of pain and hyperalgesia associated with injury and inflammation. Psychophysical studies were conducted in a patient with complete kininogen deficiency to determine whether the absence of bradykinin was associated with abnormalities in pain sensibility. Pain evoked by heat stimuli to the thenar eminence was tested before and after a localized burn, which has been shown to cause hyperalgesia in normal subjects. In addition, pain evoked by intradermal administration of bradykinin (0.1–10 μg) to the forearm and the effects of bradykinin on pain induced by heat stimuli were studied. The patient rated the intensity of pain evoked by all heat stimuli relative to the pain induced by a 3s 45°C stimulus.
2. The patient's heat pain threshold (45°C) in the glabrous skin was similar to that of age-matched control subjects (n = 5) and to that previously observed in younger control subjects.
3. The burn resulted in a decrease in pain threshold and an increase in pain induced by suprathreshold stimuli. The magnitude of hyperalgesia was within the range observed in the age-matched control subjects and in younger control subjects. Thus, kinins are not essential for the development of hyperalgesia after heat injury.
4. In control subjects, intradermal injections of bradykinin produced pain and hyperalgesia to heat stimuli. In the patient, intradermal bradykinin injections induced minimal pain and no hyperalgesia to heat stimuli. Thus, congenital absence of kininogens may be associated with a deficiency in bradykinin receptors.
Nyctohemeral changes in bone turnover assessed by serum bone Gla-protein concentration and urinary deoxypyridinoline excretion: effects of growth and ageing
Authors: Eastell Richard , Simmons Patricia S. , Colwell Antony , Assiri Adel M. A. , Burritt Mary F. , Graham R. , Russell G. , Riggs B. Lawrence 
Published: August 2015

1. To investigate whether there is a nyctohemeral rhythm in bone turnover, we measured serum bone Gla-protein (osteocalcin, an index of osteoblast activity) concentration every 2 h and urinary deoxypyridinoline (a marker of bone collagen resorption) excretion for 8 h periods in 10 pubertal girls (aged 10–14 years), 15 premenopausal women (aged 20–49 years) and 17 postmenopausal women (aged 50–75 years).
2. The serum concentration of bone Gla-protein and the urinary excretion of deoxypyridinoline were five times higher in the pubertal girls than in the premenopausal women. The urinary excretion of deoxypyridinoline in the postmenopausal women was twice that in the premenopausal women.
3. There was a nyctohemeral pattern in all age groups with mean night-time increases of 28% (P&lt;0.001) in the urinary excretion of deoxypyridinoline and of 5% (P&lt;0.001) in the serum bone Gla-protein concentration.
4. There also were nyctohemeral patterns in the urinary excretion of calcium (P&lt;0.02), sodium (P&lt;0.001) and potassium (P&lt;0.001), with decreases at night. There was a negative correlation between the night-time changes in the urinary excretion of deoxypyridinoline and calcium, especially in adult women (P&lt;0.01).
5. The serum level of parathyroid hormone increased with age, but this effect was only observed at night (01.00 to 07.00 hours). There was a nyctohemeral rhythm of the serum intact parathyroid hormone level at all ages, with a peak in the afternoon and night.
6. Thus, at night, there is a large increase in bone resorption and a small increase in osteoblastic activity, representing a nyctohemeral rhythm of bone turnover. Although the amplitudes of bone formation and bone resorption are greater during growth, the pattern of nyctohemeral changes present during growth continues up to the age of 75 years.
Spontaneous release of interleukin-1 and interleukin-6 by peripheral blood mononuclear cells after oophorectomy
Authors: Pioli Giulio , Basini Guiseppina , Pedrazzoni Mario , Musetti Giovanni , Ulietti Vittorio , Bresciani Donatella , Villa Paola , Bacchi Alberto , Hughe David , Russell Graham , Passeri Mario 
Published: August 2015

1. We studied the changes in interleukin-1 and interleukin-6 secretion by peripheral blood mononuclear cells from 12 premenopausal women after oophorectomy and seven premenopausal women who had undergone simple hysterectomy.
2. The results showed that 1 month after surgery interleukin-1 secretion increased by 414 ± 171% (mean ± sem) and interleukin-6 secretion increased by 1354 ± 481% in oophorectomized women, whereas only non-significant fluctuations in the secretion of both cytokines (−9% ± 29% for interleukin-1 and −31% ± 19% for interleukin-6) were seen in the women who had undergone simple hysterectomy. The difference between the two groups was significant (P= 0.035 for interleukin-1 and P = 0.003 for interleukin-6). In addition, oophorectomy, but not simple hysterectomy, was followed by significant increases in plasma ionized calcium concentration (P&lt;0.05), plasma alkaline phosphatase activity (P&lt;0.01) and plasma osteocalcin concentration (P&lt;0.02), and a reduction in plasma parathyroid hormone level (P&lt;0.01).
3. We conclude that ovary ablation may modify cytokine secretion by peripheral blood mononuclear cells. If this phenomenon occurs in the bone micro-environment, it could be important in the loss of bone observed after oophorectomy. However, the possibility of an independent alteration induced by the lack of gonadal hormones but unrelated to bone turnover cannot be excluded.
Effects of the angiotensin II receptor antagonist Losartan (DuP 753/MK 954) on arterial blood pressure, heart rate, plasma concentrations of angiotensin II and renin and the pressor response to infused angiotensin II in the salt-deplete dog
Authors: MacFadyen R. J. , Tree M. , Lever A. F. , Reid J. L. 
Published: August 2015

1. The blood pressure, heart rate, hormonal and pressor responses to constant rate infusion of various doses of the angiotensin (type 1) receptor antagonist Losartan (DuP 753/MK 954) were studied in the conscious salt-deplete dog.
2. Doses in the range 0.1–3 μmin−1 kg−1 caused no change in blood pressure, heart rate or pressor response to angiotensin II (54 ng min−1kg−1), and a dose of 10 μgmin−1 kg−1 had no effect on blood pressure, but caused a small fall in the pressor response to angiotensin II. Infusion of Losartan at 30 μmin−1 kg−1 for 3 h caused a fall in mean blood arterial pressure from baseline (110.9 ± 11.2 to 95.0 ± 12.8 mmHg) and a rise in heart rate (from 84.6 ± 15.1 to 103 ± 15.2 beats/min). Baseline plasma angiotensin II (42.5 ± 11.8 pg/ml) and renin (64.5 ± 92.7 μ-units/ml) concentrations were already elevated in response to salt depletion and rose significantly after Losartan infusion to reach a plateau by 70 min. The rise in mean arterial blood pressure after a test infusion of angiotensin II (35.3 ± 11.6 mmHg) was reduced at 15 min (11.8 ± 6.8 mmHg) by Losartan and fell progressively with continued infusion (3 h, 4.3 ± 3.3 mmHg). The peak plasma angiotensin II concentration during infusion of angiotensin II was unaffected by Losartan, but the rise in plasma angiotensin II concentration during infusion was reduced because of the elevated background concentration. Noradrenaline infusion caused a dose-related rise in mean blood arterial pressure (1000 ngmin−1kg−1, +19.9 ± 8 mmHg; 2000ngmin−1 kg−1, +52.8 ± 13.9 mmHg) with a fall in heart rate (1000 ng min−1 kg−1, −27.9 ± 11.5 beats/min; 2000 ng min−1 kg−1, −31.2 ± 17.3 beats/min). During Losartan infusion the 1000 but not the 2000 ng min−1 kg−1 noradrenaline infusion caused a greater rise in mean arterial blood pressure and a greater fall in heart rate. The fall in heart rate tended to decrease with continued infusion of Losartan. Plasma catecholamine concentrations were unaffected by Losartan. In a further study, higher doses of Losartan (100, 300 and 1000 μg min−1 kg−1; 30 min) produced greater falls in mean arterial blood pressure also with a rise in heart rate and complete blockade of the pressor effect of infused angiotensin II. Some animals became disturbed at the highest dose. 3. Losartan produces rapid dose-related falls in blood pressure and a rise in heart rate and renin release with elevation of plasma angiotensin II. Pressor responses to angiotensin II are reduced at intermediate doses and are eliminated at high doses. Losartan does not appear to inhibit angiotensin II clearance from the plasma and may in some way increase it.
Effects of acute NaCl, KCl and KHCO3 loads on renal electrolyte excretion in humans
Authors: van Buren Marjolijn , Rabelink Ton J. , van Rijn Herman J. M. , Koomans Hein A. 
Published: August 2015

1. Potassium salts increase sodium excretion in humans. To define the role of the potassium ion in this effect, we compared the effects of equimolar single oral loads of 100 mmol of NaCl and KCl on renal electrolyte excretion in seven healthy subjects. In a second group (n = 7), we infused equimolar loads of NaCl or KCl (0.75 mmol/kg in 2 h).
2. In both experiments the KCl load quickly increased plasma potassium and aldosterone concentrations and potassium and sodium excretion to a maximum by 2 h after the load, whereas the NaCl load had no such effect.
3. In a third group (n = 7) we compared the effects of single oral loads of KCl and KHCO3 (1 mmol/kg), to assess the role of the anion in the natriuretic effect of potassium salts.
4. KCl and KHCO3 transiently stimulated urinary excretion of potassium and sodium in an identical manner.
5. We also followed the changes in acid excretion over time. Whereas both KCl and KHCO3 loading decreased acid excretion, this effect was greater after KHCO3 loading. Interestingly, acid excretion did not decrease further after the first collection hour after the potassium load, although the plasma potassium concentration was still increasing.
6. From these data we conclude (1) that increased excretion of sodium, potassium and chloride and decreased excretion of protons after administration of potassium salts are the specific effects of the potassium component; (2) that potassium also appears to have secondary, indirect effects on proton excretion, the mechanism of which remains to be clarified.