bluuebunny/crossref_metadata_2025 huggingface dataset:
Antihypertensive and renal effects of cilazapril and their reversal by angiotensin in renovascular hypertensive rats
Authors: Ding Yu-An , Chang Shin-Tsu , Shieh Shyh-Ming , Huang Wann-Chu
Published: August 2015

1. The antihypertensive and renal effects of cilazapril, a new angiotensin converting enzyme inhibitor, were evaluated in both two-kidney, one-clip Goldblatt hypertensive rats (n = 11) and normotensive rats (n = 6).

2. Intravenous infusion of cilazapril (1 mg/kg followed by 25 μg min−1 kg−1) caused significant reductions of blood pressure from 163 ± 3 to 122 ± 4 mmHg and from 157 ± 2 to 113 ± 3 mmHg in two separate groups of hypertensive rats and from 124 ± 1 to 105 ± 2 mmHg in normotensive rats. The hypotensive effect in terms of absolute value or percentage change was greater in hypertensive rats than in normotensive rats (41 ± 6 vs 20 ± 3 mmHg or 25 ± 4% vs 16 ± 2%, respectively).

3. Cilazapril increased glomerular filtration rate, urine flow, and absolute and fractional excretion rates of sodium and potassium in the non-clipped kidney of hypertensive rats. In contrast, the clipped kidney exhibited a depressed renal function during cilazapril infusion.

4. In normotensive rats, the hypotensive and enhanced renal function responses to cilazapril were much less than those of the non-clipped kidney of hypertensive rats.

5. Superimposed administration of either angiotensin II or angiotensin III during cilazapril infusion completely reversed the blood pressure and bilateral renal responses of cilazapril in both hypertensive and normotensive rats.

6. These results indicate that cilazapril reduces arterial pressure and enhances renal excretion mainly via inhibition of angiotensin II and angiotensin III formation.
Effect of hyperoxia and hypoxia on exercise-induced breathlessness in normal subjects
Authors: Chronos N. , Adams L. , Guz A.
Published: August 2015

1. The subjective changes accompanying alterations in inspired oxygen concentration during heavy exercise have been investigated single blind, in normal subjects.

2. In particular, the intensity of the sensation of breathlessness was quantified using a visual analogue scale and changes were compared with those in objective ventilatory measures.

3. Eleven subjects performed three steady-state workload exercise tests on different days and 100% O2, 15% O2 or air were randomly administered for a fixed interval during each test.

4. Compared with air breathing, all subjects felt less breathless during 100% O2 breathing, and ten of them felt more breathless when inspiring 15% O2; these changes were reversed on return to air breathing.

5. During and after 100% O2, the time course of changes in breathlessness was similar to those for ear arterial oxygen saturation and minute ventilation such that it could be a secondary response to either. However, during and after inspiration of 15% O2, changes in breathlessness occurred relatively more quickly than those in ventilation, more closely reflecting changes in oxygen saturation; this suggests that hypoxia, per se, could contribute to the genesis of this sensation.

6. Individual variability in breathlessness responses to exercise and changes in inspired oxygen concentration did not correlate with objective ventilatory changes; neither were changes in breathlessness in the group particularly associated with changes in respiratory frequency or tidal volume.
Osmoregulation of thirst and vasopressin secretion in insulin-dependent diabetes mellitus
Authors: Thompson C. J. , Davis S. N. , Butler P. C. , Charlton J. A. , Baylis P. H.
Published: August 2015

1. Osmotically stimulated thirst and vasopressin release were studied during infusions of hypertonic sodium chloride and hypertonic d-glucose in euglycaemic clamped diabetic patients and healthy controls.

2. Infusion of hypertonic sodium chloride caused similar elevations of plasma osmolality in diabetic patients (288.0 ± 1.0 to 304.1 ± 1.6 mosmol/kg, mean ± sem, P < 0.001) and controls (288.6 ± 0.9 to 305.7 ± 0.6 mosmol/kg, P < 0.001), accompanied by progressive increases in plasma vasopressin (diabetic patients, 0.9 ± 0.3 to 7.7 ± 1.5 pmol/l, P < 0.001; controls 0.5 ± 0.1 to 6.5 ± 1.0 pmol/l, P < 0.001) and thirst ratings (diabetic patients 1.0 ± 0.2 to 7.1 ± 0.5 cm, P < 0.001; controls 1.8 ± 0.4 to 8.0 ± 0.5 cm, P < 0.001) in both groups.

3. Drinking rapidly abolished thirst and vasopressin secretion before major changes in plasma osmolality occurred in both diabetic patients and healthy controls.

4. There were close and significant correlations between plasma vasopressin and plasma osmolality (diabetic patients, r = + 0.89, controls r = + 0.93) and between thirst and plasma osmolality (diabetic patients r = +0.95, controls r = +0.97) in both diabetic patients and healthy controls during hypertonic saline infusion.

5. Hypertonic d-glucose infusion caused similar elevations in blood glucose in diabetic patients (4.0 ± 0.2 to 20.1 ± 1.2 mmol/l, P < 0.001) and healthy controls (4.3 ± 0.1 to 19.3 ± 1.2 mmol/l, P < 0.001) but did not change plasma vasopressin or thirst ratings. There was no correlation between plasma osmolality and either thirst or plasma vasopressin during hypertonic d-glucose infusion.

6. The characteristics of osmoregulated thirst and vasopressin release are similar in health and diabetes mellitus. As hyperglycaemia was not dipsogenic, however, the thirst of poorly controlled diabetes mellitus may be due to hypovolaemia secondary to polyuria rather than hyperosmolality due to elevated blood glucose concentrations.
Prostaglandin precursor fatty acids in cirrhosis with ascites: Effect of linoleic acid infusion in functional renal failure
Authors: Rimola Antoni , Ginés Pere , Cusó Eulàlia , Camps Jordi , Gaya Joan , Arroyo Vincente , Rodés Joan
Published: August 2015

1. Functional renal failure (FRF) in cirrhosis with ascites could be related to an inappropriately low renal prostaglandin (PG) production. To investigate whether the impaired renal PG synthesis in these patients is related to a PG precursor fatty acid deficiency, serum levels of linoleic and arachidonic acids and the urinary excretion of PGE2, 6-keto-PGF1α and thromboxane B2 (TxB2) were measured in 10 normal subjects, 17 non-azotaemic cirrhotic patients with ascites and 10 cirrhotic patients with ascites and FRF.

2. Serum linoleic acid levels were similar in the three groups studied. Both groups of cirrhotic patients showed lower arachidonic acid levels than normal subjects; however, non-azotaemic cirrhotic patients and patients with FRF did not differ in relation to serum arachidonic acid.

3. Non-azotaemic cirrhotic patients had higher urinary PGE2, 6-keto-PGF1α and TxB2 excretion than normal subjects and cirrhotic patients with FRF. Patients with FRF showed similar urinary PGE2 and TxB2 and lower urinary 6-keto-PGF1α than normal subjects. In all cirrhotic patients no significant correlation was found between serum linoleic and arachidonic acid levels and urinary PGs.

4. In seven patients with FRF an acute intravenous infusion of linoleic acid induced a marked increase in serum levels of this fatty acid. However, no increase in serum arachidonic acid levels and urinary PG excretion and no improvement in renal function was observed.

5. This study suggests that an arachidonic acid deficiency is present in cirrhotic patients with ascites but that this abnormality is not a major determinant of renal function and PG production in these patients. Acute intravenous administration of linoleic acid is not associated with any change in renal PG production and renal function in cirrhotic patients with FRF.
Detection of brown adipose tissue uncoupling protein mRNA in adult patients by a human genomic probe
Authors: Bouillaud Frédéric , Villarroya Francesc , Hentz Eliane , Raimbault Serge , Cassard Anne-Marie , Ricquier Daniel
Published: August 2015

1. Studies on human brown adipose tissue require specific molecular probes. A human genomic library has been screened with a complementary DNA corresponding to the uncoupling protein (UCP) of rat brown adipose tissue mitochondria.

2. Two recombinant phages were isolated, carrying genomic sequences of human UCP. From them we have subcloned a 0.5 kilobase fragment. This fragment, H-Ucp-0.5, contained two intronic regions and two exonic regions. Exonic regions encoded a sequence of 84 amino acids which exhibited a strong homology with central domain at rat UCP. The organization of H-Ucp-0.5 was confirmed by SI mapping analysis.

3. A Southern analysis suggested that the gene is single type in the human, as it is in rodents.

4. In Northern analysis experiments, H-Ucp-0.5 detected a specific 1.8 kb mRNA in human brown adipose tissue obtained from six patients with phaeochromocytoma and from one patient with a hibernoma. This molecular probe is a new, sensitive and reliable tool with which to study human brown adipocytes.
Investigation of serum creatine kinase variability after muscle-damaging exercise
Authors: Clarkson Priscilla M. , Ebbeling Cara
Published: August 2015

1. The present study examined if the presence of creatine kinase (CK) inhibitors might explain the large variability in blood levels of CK among subjects after exercise-induced muscle damage.

2. Twenty-four women performed an eccentric exercise with the forearm flexors and were then classified as no CK responders, low CK responders and high CK responders. High CK responders repeated the exercise two weeks later (bout two).

3. Sera from high CK responders were mixed with sera from no CK responders or low CK responders. Also, serum from high CK responders obtained after bout one was mixed with the same subject's serum from after bout two.

4. In all cases, the differences between the expected and observed CK activity for the mixes were within the expected variability for the assay.

5. Although CK inhibitors have been previously observed in sera from patients with muscle injury or disease, we were unable to demonstrate the presence of CK inhibitors in the sera from subjects who showed evidence of exercise-induced muscle damage.
Longitudinal study of renal prostaglandin excretion in cirrhotic rats: Relationship with the renin–aldosterone system
Authors: Solá Javier , Camps Jordi , Arroyo Vicente , Guarner Francisco , Gaya Joan , Rivera Francisca , Rodes Joan
Published: August 2015

1. A cross-sectional study (protocol A) was performed in 19 rats with cirrhosis, induced by carbon tetrachloride (CCl4), and ascites and in 10 control animals to assess renal prostaglandin (PG) excretion in experimental cirrhosis. In an additional group of animals, including nine rats chronically exposed to CCl4 (CCl4 rats) and six control rats, a longitudinal study (protocol B) was performed to investigate the temporal relationship between changes in renal PG excretion, the renin—aldosterone system and renal function.

2. Urinary PG excretion was assessed by specific radioimmunoassay of PGE2, PGF2α, 6-keto-PGF1α and thromboxane (TX) B2 after extraction with octadecyl silica cartridges and h.p.l.c. purification. Recoveries for each prostanoid (61 ± 8% for PGE2, 64 ± 12% for PGF2α, 65 ±11% for 6-keto-PGF1α and 66 ±17% for TXB2) were determined in every sample by adding tritiated standards, and the final values were corrected according to the individual recoveries.

3. Cirrhotic rats with ascites in protocol A showed a significantly higher plasma renin and aldosterone concentrations and urinary excretion of 6-keto-PGF1α and TXB2 than did control animals. Urinary excretion of PGE2 and PGF2α, however, was significantly reduced in cirrhotic animals as compared with controls.

4. In CCl4 rats included in protocol B, there was a close chronological relationship between the activation of the renin-aldosterone system, as estimated by urinary aldosterone excretion, the onset of sodium retention and the increase in urinary excretion of 6-keto-PGF1α and TXB2. The urinary excretion of PGE2 and PGF2α in CCl4 rats was reduced throughout the study.

5. These results suggest that in rats with CCl4-induced cirrhosis, the increased renal production of prostacyclin and TXA2 is a consequence of the stimulation of endogenous vasoconstrictor systems. The impaired urinary excretion of PGE2 and PGF2α in CCl4 rats may be secondary to an inhibitory effect of CCl4 on PG synthesis in the renal tubules.
Muscle and bone in paraplegic patients, and the effect of functional electrical stimulation
Authors: Pacy P. J. , Hesp R. , Halliday D. A. , Katz D. , Cameron Gillian , Reeve J.
Published: August 2015

1. Four paraplegic men volunteered for an exercise programme in which their paralysed quadriceps muscles were stimulated by means of computer-regulated electrical impulses applied through external electrodes. The first exercise regimen consisted of leg raising against a graded load, and during the second regimen exercise took the form of cycling on a modified bicycle ergometer. Each subject exercised five times weekly for 10 weeks during the first regimen and 32 weeks during the second regimen.

2. Whole-body protein turnover determined by l-[1-13C]leucine during feeding remained constant during both exercise regimens, when expressed either in terms of body weight or fat-free mass derived from measurements of total body potassium.

3. Quadriceps muscle protein synthetic rate increased during the study, from 0.0712 to 0.0985%/h (P < 0.05), as did quadriceps muscle area assessed by computed tomography.

4. Bone mineral content for lumbar vertebrae was normal in all four patients, but for the femoral mid-shaft bone mineral content averaged only 66% of normal for three of the patients. Trabecular bone density in the distal tibia ranged from normal to 2% of normal for the men with the shortest and longest periods of disability, respectively. No changes in bone mineral content or bone density occurred during the exercise period.
Atrial natriuretic peptide vascular receptor: regulation of low-affinity binding by calcium
Authors: Morton J. J. , Beattie Elisabeth C. , Lyall Fiona
Published: August 2015

1. In the presence of calcium, both high- [dissociation equilibrium constant (Kd) 5.8 × 10−11 mol/l] and low-(Kd 1.2 × 10−8 mol/l) affinity binding of atrial natriuretic peptide was detected on plasma membranes prepared from sodium-depleted rats.

2. In contrast, under calcium-free conditions only high-affinity binding (Kd 6.9 × 10−11 mol/l) was detected.

3. The requirement for calcium for low-affinity binding suggests a different mechanism of action than that for the high-affinity receptor.
Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes
Authors: Zorzano Antonio , del Arbol Luis Ruiz , Herrera Emilio
Published: August 2015

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1. 2. 1. 3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects.

2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities.

3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group.

4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group.

5. Hepatic ALDH activity, assayed at 300 μmol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.

6. In summary, our data demonstrate that (a) marked modifications in ADH activity, as found in patients with atypical ADH or in subjects with alcoholic liver disease, are not accompanied by parallel alterations in the kinetics of ethanol disappearance, suggesting that ADH activity per se does not limit ethanol metabolism in vivo, (b) hepatic high-Km ALDH activity is decreased in patients with liver disease independent of alcoholism, and therefore decreased ALDH activity cannot be considered as a primary defect in alcoholism but as a consequence of liver damage, and (c) erythrocyte ALDH does not reflect hepatic high-Km ALDH.
Atrial natriuretic peptide: physiological release associated with natriuresis during negative pressure breathing in man
Authors: Anderson J. V. , Maxwell D. L. , Payne N. N. , Slater J. D. H. , Bloom S. R.
Published: August 2015

1. Negative pressure breathing was one of the first physiological tools used to study the renal effects of redistribution of the blood volume from the peripheries to the thorax. The recent discovery of a putative natriuretic hormone (atrial natriuretic peptide, ANP) in cardiac atrial tissue has rekindled interest in the effect of the cardiovascular system on renal function. We have therefore studied the effects of this physiological manoeuvre on plasma ANP concentrations and renal responses.

2. Plasma concentrations of ANP, plasma renin activity and plasma aldosterone concentration were measured during an 80 min period of negative pressure breathing at −12 cmH2O pressure in six hydrated normal subjects. Identical control studies were performed in the same subjects at at least 1 week apart.

3. Negative pressure breathing resulted in a natriuresis and diuresis which were associated with a significant rise in plasma ANP concentration. The natriuresis occurred despite an increase in plasma renin activity and in plasma aldosterone concentration.

4. These findings, under specific carefully controlled conditions, support the previously contentious postulate that negative pressure breathing enhances sodium excretion, in addition to its well-recognized diuretic effect. They add further weight to the hypothesis that expansion of the central blood volume is an important stimulus to the release of ANP from the heart (acting by way of atrial distension), and suggest that changes of plasma ANP concentration may have induced the natriuresis which occurred in the face of a modest activation of the sodium-retaining renin-aldosterone system.
Increase in Proteinuria and Reduction in Number of Anionic Sites on the Glomerular Basement Membrane in Rabbits by Infusion of Human Nephrotic Plasma in Vivo
Authors: Wilkinson Alan H. , Gillespie Cecilia , Hartley Barry , Williams D. Gwyn
Published: August 2015

1. Intraortic suprarenal infusion in vivo of New Zealand White rabbits with plasma from patients with the nephrotic syndrome reduced the number of anionic sites labelled by the cationic polymer polyethyleneimine in the lamina rara iterna to 14.0 ± 2.7 per 1000 nm of lamina rara interna (mean ± sd) compared with 18.7 ± 2.1 (P < 0.005) after infusion of plasma from normal subjects.

2. Proteinuria increased in all nine animals infused with nephrotic plasma and in two of seven infused with control plasma (P < 0.01). The mean increase in proteinuria in the animals infused with nephrotic plasma was 246 mg/l (P < 0.05), whereas in those infused with control plasma there was no increase.

3. We conclude that nephrotic plasma contains a factor(s) capable of neutralizing the charge of these anionic sites and concomitantly increasing proteinuria.
Effect of Phosphate-Buffered Sucrose Flush Solution upon the Initial Phase of Ischaemic Acute Renal Failure in the Rat
Authors: Ferwana O. S. , Pirie S. C. , Potts D. J.
Published: August 2015

1. Experiments were performed upon anaesthetized rats to investigate the effect upon the initial 4 h of ischaemic acute renal failure of intrarenal flush with phosphate buffer (PB), sucrose alone and phosphate-buffered sucrose (PBS) solutions of differing compositions.

2. Kidneys flushed with PB immediately before 45 min pedicle clamp ischaemia exhibited a post-ischaemic function similar to that of control, non-flushed kidneys: they were isosthenuric and non-oliguric with a clearance of inulin (Cin) depressed to 10% of the pre-ischaemic value.

3. Kidneys flushed with 50 mmol/l sucrose in saline before ischaemia became isosthenuric, oliguric and had a more severely depressed post-ischaemic Cin compared with non-flushed kidneys.

4. Kidneys flushed with PBS containing either 50 (PBS50) or 140 (PBS140) mmol/l sucrose at pH 7 became polyuric after ischaemia, produced concentrated urine and had Cin values significantly higher than control kidneys.

5. Raising the pH of the PBS50 to 7.4 resulted in isosthenuric, polyuric kidneys that had a post-ischaemic Cin not significantly different from that of the control group.

6. It is concluded that the severity of the initial phase of ischaemic acute renal failure was significantly reduced by intrarenal flush with a PBS solution of pH 7; flush with PB or sucrose alone had no protective action.
A Comparison of Some Thermoregulatory Responses in Healthy Children and in Children with Burn Injury
Authors: Childs C. , Stoner H. B. , Little R. A. , Davenport P. J.
Published: August 2015

1. Changes in body heat content in five normal adults, in 30 healthy children and in 24 children who had suffered burn injury 1–5 h previously, have been studied in cool (20°C) and warm (30°C) environments.

2. On moving from a cool to a warm environment, the heat content rose in both normal adults and healthy children, but the increase was significantly larger in the children.

3. Much larger changes occurred in the burned children in whom the heat content rose to a new plateau within about 8 h of the accident.

4. The changes after burn injury were unrelated to the bandaging of the burn and were little affected by the environmental temperature.
Prevention of Glucose-Induced Hypotension by the Somatostatin Analogue Octreotide (Sms 201-995) in Chronic Autonomic Failure: Haemodynamic and Hormonal Changes
Authors: Raimbach S. J. , Cortelli P. , Kooner J. S. , Bannister R. , Bloom S. R. , Mathias C. J.
Published: August 2015

1. The haemodynamic and hormonal changes following glucose ingestion (1 g/kg) were determined before and after pretreatment with either placebo or the somatostatin analogue, octreotide (SMS 201-995, 50 μg sub-cutaneously), in seven patients with chronic autonomic failure

2. In the placebo phase, after glucose, there was a marked and prolonged fall in blood pressure with no change in cardiac index and peripheral blood flow. Plasma insulin and neurotensin levels increased, whereas glucagon, vasoactive intestinal polypeptide, noradrenaline and adrenaline levels were unchanged

3. Octreotide transiently raised blood pressure and prevented glucose-induced hypotension. There were no changes in cardiac index or peripheral blood flow. Plasma insulin and neurotensin levels did not rise. Plasma glucose levels increased more slowly but reached a similar level to the placebo phase

4. We conclude that in autonomic failure patients, glucose-induced hypotension was not accompanied by changes in cardiac index or peripheral blood flow, indicating a lack of compensation to probable splanchnic vasodilatation. The hypotension was prevented by the peptide release inhibitor, octreotide, with no change in cardiac index or in peripheral blood flow, suggesting an effect on the splanchnic vasculature, probably through inhibiting release of vasodilatatory pancreatic and gut peptides.
Genetic variation on chromosome 16 is associated with abdominal aortic aneurysm
Authors: Powell Janet T. , Bashir Arshad , Dawson Sally , Vine Nicholas , Henney Adriano M. , Humphries Stephen E. , Greenhalgh Roger M.
Published: August 2015

1. There is a familial tendency to abdominal aortic aneurysms. We have followed up a previous report of a weak association between the haptoglobin 2-1 phenotype and aortic aneurysm and investigated polymorphisms of the haptoglobin gene and neighbouring cholesterol ester transfer protein gene on the long arm of chromosome 16 in patients with atherosclerotic abdominal aortic aneurysm, patients with stenosing aortic atherosclerosis and healthy control subjects. The protein polymorphism of haptoglobin results from variant α-chains, α1 and α2, the phenotype nomenclature describing the two α-chains. We have also investigated whether the different haptoglobin phenotypes influence the degradation of aortic connective tissue.

2. The frequency of the haptoglobin α1 allele was increased in patients with aneurysms compared with healthy control subjects (0.51 versus 0.35, P < 0.05). Patients homozygous for the α2 allele had the highest mean age at aneurysm resection. The frequency of a rare polymorphism at the cholesterol ester transfer protein locus was also increased in aneurysm patients (0.15 versus 0.05 in control subjects, P < 0.01). These two genetic markers appear to act independently. Haptoglobins containing an α1-chain accelerated two-to fourfold the degradation by elastases of aortic elastin in vitro.

3. Genetic variation in the haptoglobin and cholesterol ester transfer protein genes appears to influence dilatation of the abdominal aorta. Variation at the haptoglobin locus could have a direct effect on the degradation of elastin in atherosclerotic aorta, whereas variation at the cholesterol ester transfer protein locus could affect lipid metabolism and promote atherosclerosis. These results indicate that a gene on chromosome 16 is associated with aortic aneurysm, although this may be an as yet unidentified gene in linkage disequilibrium with the haptoglobin and cholesterol ester transfer protein genes.
Pre-replicative phase-related changes in bile acid-induced choleresis in the regenerating rat liver
Authors: Garcia-Marin J. J. , Regueiro P. , Perez-Antona J. C. , Villanueva G. R. , Perez-Barriocanal F.
Published: August 2015

1. During the pre-replicative phase of the regenerating rat liver some interesting changes occur, which might selectively modify some mechanisms involved in bile formation, such as those responsible for the hypercholeretic effect of ursodeoxycholic acid. The aim of the present work was to gain information on this point.

2. Anaesthetized male Wistar rats (∼ 250 g) were used. The animals underwent two-thirds hepatectomy 1, 6 or 12 h before collection of bile samples was begun. Very early after hepatectomy (1 h) spontaneous bile flow and bile acid output were increased. Both returned to values not significantly different from those of the controls at 6 h. Bile flow increased again at the end of the pre-replicative phase. Taurocholate infusion (200 nmol min−1 g−1 calculated liver weight) induced increases in bile flow and bile acid output that were similar in both the control and hepatectomized rats, regardless of the time of the pre-replicative phase considered.

3. Cholic acid and ursodeoxycholic acid were infused (300 nmol min−1 g−1 calculated liver weight) into control and partially hepatectomized rats (at the mid-point of the pre-replicative phase, i.e. 6 h after surgical liver resection). Cholic acid-induced bile flow, bile acid and bicarbonate output expressed per g of remaining liver were similar in control and in hepatectomized rats. By contrast, ursodeoxycholic acid-induced choleresis was profoundly altered during the pre-replicative phase. As expressed per g of remaining liver, bile flow was markedly reduced (− 17%, P < 0.05), in spite of total bile acid output being greatly increased (+ 148%, P < 0.001). The reduced choleretic effect of ursodeoxycholic acid may be due to a lowered stimulation of bicarbonate secretion (− 41%, P < 0.01).

4. Factors known to reduce ursodeoxycholic acid-induced bicarbonate secretion into bile, such as decreased plasma bicarbonate concentrations and lowered total hepatic carbonic anhydrase activity, cannot account for the loss of the ability of ursodeoxycholic acid to stimulate bicarbonate secretion during the pre-replicative phase. However, the bile acid conjugation patterns were dramatically altered early after hepatectomy (6 h). In bile from the control animals the major ursodeoxycholic acid conjugation was with glycine, whereas in hepatectomized rats it was with taurine.

5. In summary, our results indicate that during the prereplicative phase of the regenerating rat liver, a loss occurs in the hypercholeretic effect of bile acids such as ursodeoxycholic acid. However, the choleretic effect of non-hypercholeretic bile acids such as cholic acid and taurocholic acid was not altered. Moreover, the existence of a relationship between the decrease in bile flow and bicarbonate output and the marked increase in the secretion of low-pKa conjugated bile acid derivatives is suggested.
Influence of raising maternal blood pressure with angiotensin II on utero-placental and feto-placental blood velocity indices in the human
Authors: Loquet Ph. , Pipkin F. Broughton , Symonds E. M. , Rubin P. C.
Published: August 2015

1. The effect of doubling doses of angiotensin II on maternal systemic blood pressure and arcuate and fetal umbilical artery Doppler velocity profiles has been investigated in 10 women in first- and 10 in second-trimester pregnancy. Ten non-pregnant women were also studied.

2. A progressive decrease in the pressor response to angiotensin II in early pregnancy as previously described was confirmed.

3. Angiotensin II induced a significant dose-dependent increase in the pulsatility index (a measure of downstream resistance) in the umbilical artery in both first- and second-trimester patients. There was an apparent increase in the threshold response of the pulsatility index to angiotensin II in the umbilical artery as pregnancy progressed. There was also a significant correlation between changes in maternal systolic or diastolic pressure and change in umbilical artery pulsatility index, but this did not differ between the two trimesters. This suggests that the increase in pulsatility index is related to blood pressure rather than angiotensin II. This is consistent with reports that angiotensin II does not cross the haemo-monochorial placenta.

4. Basal pulsatility index in the arcuate artery fell with increasing gestation. There was a significant inverse association between the evoked change in maternal systemic blood pressure and the change in arcuate artery pulsatility index, suggesting local vasodilatation.

5. We conclude that acutely increasing maternal blood pressure leads to increased vascular resistance on the fetal side of the circulation.
Urinary prostaglandin F2α excretion is not pH-dependent in the conscious rat: implications for the urinary prostaglandin E2/prostaglandin F2α ratio
Authors: Haylor J. , Lote C. J.
Published: August 2015

1. The influence of urine pH on the urinary excretion of prostaglandin (PG) F2α and the PGE2/PGF2α ratio has been examined in the conscious rat.

2. The basal urinary PGF2α excretion rate of 3.9 pmol/h (n = 23) did not vary with urine pH. In marked contrast, PGE2 excretion increased as the urine became more alkaline. The PGE2/PGF2α ratio therefore progressively increased from 1.5 to 22 as the pH of the urine changed from pH 5.8 to pH 7.8.

3. The independence of PGF2α excretion from urine pH: (a) excludes cyclo-oxygenase as a potential site of action for the pH-dependence of urinary PGE2 excretion; (b) suggests that the urinary PGE2/PGF2α ratio measured in alkaline urine may be a more accurate reflection of the kidneys, ability to synthesize these two prostaglandins in vivo; (c) suggests that control of urine pH is required before the urinary PGE2/PGF2α ratio can be employed as an index of PGE2 9-ketoreductase (EC 1.1.1.189) activity in vivo.
Importance of inspiratory flow rate in the cough response to citric acid inhalation in normal subjects
Authors: Barros Manuel J. , Zammattio Stefano J. , Rees P. John
Published: August 2015

1. The cough response to inhalation of citric acid is produced mainly by irritation of the larynx and trachea. Variations in the inspiratory flow rate might lead to changes in deposition of the drug, and consequently in the cough threshold.

2. We have studied the effect of three different inspiratory flow rates in 11 normal, non-smoking subjects (nine males, aged 23–39 years), who inhaled nebulized citric acid (2.5–640 mg/l). The test finished when a cough. was produced at each inhalation (cough threshold) or the maximum concentration was reached.

3. The inspiratory flow rate was limited with a fixed resistance and displayed on a screen so that the subjects could reach a constant inspiratory flow rate of 50, 100 and 150 l/min with a submaximal inspiratory effort.

4. The mean (sd) inspiratory flow rates achieved were 51.4 (5.3), 86.2 (16.6) and 134.4 (22.9) l/min. Baseline forced expiratory volume in 1 s and functional vital capacity were not different on the 3 study days.

5. The cough threshold (geometric mean and 95% confidence intervals) was 21 (9–54) mg/l at an inspiratory flow rate of 50 l/min and 43 (13–141) mg/l at 150 l/min (P <0.05). The amount of drug tolerated by the subjects before the cough threshold was achieved was 5.2 (2.0–13.8) mg at an inspiratory flow rate of 50 l/min and 11.6 (3.4–39.8) mg at 150 l/min (P <0.05). The number of coughs per inhalation was 1.6 (1.1–2.0) at an inspiratory flow rate of 50 l/min and 1.1 (0.7–1.5) at 150 l/min (P <0.05).

6. We conclude that lower inspiratory flow rates were associated with a greater cough stimulus in the citric acid challenge procedure used in this study. This may be related to increased laryngeal deposition. The inspiratory flow rate is a variable which should be controlled in the performance of cough challenges with citric acid.
Non-Invasive Assessment of the Cardiovascular Eicosanoids, Thromboxane A2 and Prostacyclin, in Randomly Sampled Males, with Special Reference to the Influence of Inheritance and Environmental Factors
Authors: Wennmalm Å. , Benthin G. , Caidahl K. , Granström E. F. , Lanne B. , Persson L. , Petersson A.-S. , Winell S.
Published: August 2015

1. We studied, in a random sample of 385 nonsmoking men born in 1968–1969 and 31 men born in 1913 or 1923, whether inheritance and environmental factors influenced platelet activity and vessel wall prostacyclin formation, as reflected non-invasively by the urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 (2,3-dinor-thromboxane B2, Tx-M) and prostacyclin (2,3-dinor-6-keto-prostaglandin F1α, PGI-M), respectively.

2. Fathers of young men with high platelet activity did not excrete more Tx-M than fathers of young men with low platelet activity. Men born in 1913 or 1923 displayed higher Tx-M (563 versus 128 pg/mg of creatinine, P < 0.001) and PGI-M (163 versus 130 pg/mg of creatinine, P < 0.01) excretion than those born in 1968–1969. Excretion of both Tx-M and PGI-M was correlated to the urinary output of noradrenaline and adrenaline.

3. Well-trained subjects did not differ in their excretion of Tx-M or PGI-M from those who did not exercise regularly. A recent acute infection was also unrelated to the excretion of Tx-M or PGI-M. PGI-M excretion was, however, significantly correlated to Tx-M excretion (r = 0.51, P < 0.001).

4. This study provides the first non-invasive evidence that advancing age and sympathoadrenal tone are positively correlated to platelet activity in randomly sampled men, and that paternal inheritance, physical fitness and recent infection lack correlation to platelet activity.
Effect of plasma from patients with essential hypertension on vascular resistance in the isolated perfused rat kidney
Authors: Bachmann Jürgen , Schlüter Hartmut , Storkebaum Walter , Witzel Herbert , Wessels Franz , Zidek Walter
Published: August 2015

1. Isolated perfused rat kidneys were used to study the effects of plasma fractions obtained by gel filtration from essential hypertensive patients (n = 40) and from normotensive subjects (n = 36) on resistance vessels. Perfusion pressure was recorded at a constant flow.

2. Plasma fractions were obtained by gel filtration and contained substances with a molecular mass in the range 1000–1500 Da. The plasma fractions from hypertensive patients used in this study had been shown to increase blood pressure after intravenous injection in rats.

3. In the isolated rat kidneys, the hypertensive fractions increased perfusion pressure by 20 ± 17 mmHg (mean ± SD, range 5–58 mmHg, n = 40). The analogous fractions from normotensive subjects did not change perfusion pressure significantly.

4. In Ca2+-free medium containing 2 mmol/l ethyleneglycol bis-(aminoethyl ether)tetra-acetate, the change in perfusion pressure induced by active plasma fractions was reduced by 95.2 ± 6.3%. Addition of nifedipine to the perfusion medium reduced, but did not abolish, the pressure response of the kidneys.

5. In solutions containing phentolamine or saralasin, vasoconstriction was not reduced.

6. Thus in the active fractions from hypertensive plasma, a vasopressor agent with direct action on resistance vessels can be demonstrated. This substance probably acts by increasing Ca2+ influx in vascular smooth muscle cells.
Differentiation between the intensity of breathlessness and the distress it evokes in normal subjects during exercise
Authors: Wilson Rachel C. , Jones P. W.
Published: August 2015

1. This study was designed to examine whether normal subjects could differentiate between the ‘intensity’ of their breathlessness and the amount of ‘distress’ it evoked, by specific wording of the instructions.

2. A preliminary study showed no significant difference between ‘distress’ score during exercise measured on two separate occasions (P = 0.3).

3. Ten subjects each performed two identical incremental cycle-ergometer exercise tests on separate occasions during which they were asked to quantify either ‘intensity’ or ‘distress’ by using modified Borg scales.

4. In all subjects there was a significant correlation (P <0.001) between ‘intensity’ and minute ventilation. In eight subjects there was a significant correlation (P <0.05) between ‘distress’ and minute ventilation. One subject displayed no significant correlation and one registered no distress.

5. Mean ‘intensity’ was greater than the mean ‘distress’ (P = 0.0001). The slope of ‘intensity’/minute ventilation was greater than the slope of ‘distress’/minute ventilation (P = 0.0001).

6. Within individuals there was a significant correlation beween ‘intensity’ and ‘distress’ (P <0.05). There was a wide scatter in the slope of this relationship between subjects and maximum ‘intensity’ and ‘distress’ did not correlate.

7. Different elements of the breathlessness sensation could be identified and selectively measured depending on the wording of the instructions given to the subject.

8. There was a wide intersubject variation in the magnitude of both breathlessness ‘intensity’ and ‘distress’ estimates, but the differences between subjects in these two components of the sensation did not appear to follow a common pattern.
Total body calcium in patients with inflammatory bowel disease: a longitudinal study
Authors: Ryde S. J. S. , Clements D. , Evans W. D. , Motley R. , Morgan W. D. , Evans C. , Rhodes J. , Compston J. E.
Published: August 2015

1. Serial measurements of total body calcium have been made by prompt γ-neutron activation analysis in 13 patients with inflammatory bowel disease over a mean period of 23 months. Changes in spinal trabecular bone mineral density and radial shaft bone mineral content were also assessed by using quantitative computed tomography and single photon absorptiometry, respectively.

2. The mean annual decreases (95% confidence intervals) were: total body calcium, 7.8% (−12.0 to −3.7%; P <0.001); spinal trabecular bone mineral density, 2.5% (−5.0 to +0.1%; 0.05 <P <0.1), radial bone mineral content, 2.1% (−3.4 to −0.8%; P <0.01).

3. No significant correlations were found between rates of change of the three variables. However, there were significant positive correlations between the baseline values for total body calcium and radial bone mineral content (r = 0.638, P <0.05), spinal bone mineral density and radial bone mineral content (r = 0.854, P <0.01), and total body calcium and spinal bone mineral density (r = 0.876, P <0.001).

4. These results demonstrate rapid decreases in total body calcium in patients with inflammatory bowel disease which, in conjunction with the significant decrease in radial shaft bone mineral content, indicate increased rates of cortical bone loss. Whilst values for bone mass at different skeletal sites showed positive correlations within individuals, no relationship was found between the rates of change in bone mass at these sites.

5. The rapid bone loss observed in some subjects emphasizes the importance of early detection of osteoporosis by bone densitometry and the need for effective prophylactic measures to be established in this group of patients.
Autonomic mechanisms underlying intraocular pressure changes during insulin-induced hypoglycaemia in normal human subjects: effects of pharmacological blockade
Authors: Hepburn D. A. , Fisher B. M. , Thomson I. , Barrie T. , Frier B. M.
Published: August 2015

1. A fall in intraocular pressure is induced by acute hypoglycaemia in humans. The role of the autonomic nervous system in mediating this response was investigated in 24 normal volunteers in whom hypoglycaemia was induced with intravenous soluble insulin, under four experimental conditions: (1) control (n = 6), (2) nonselective α-adrenoceptor blockade (phentolamine) (n = 6), (3) non-selective β-adrenoceptor blockade (propranolol) (n = 6) and (4) cholinergic blockade (atropine) (n = 6). Intraocular pressure was measured by using an applanation tonometer. In 12 subjects intraocular pressure was measured during each type of pharmacological blockade of similar duration without induction of hypoglycaemia, to assess the effects of individual antagonists.

2. In the control study intraocular pressure fell during hypoglycaemia from 15 ± 1.0 to 10 ± 1.3 mmHg (P <0.01) 10 min after the autonomic reaction. β-Adrenoceptor blockade caused a reduction in intraocular pressure from 15 ± 1.1 to 9 ± 1.0 mmHg (P <0.001) before the administration of insulin, and when hypoglycaemia was induced intraocular pressure decreased further to 7 ± 1.0 mmHg (P <0.05, compared with immediately before insulin). A decrease in intraocular pressure of similar magnitude was observed with propranolol alone (16 ± 1.0 to 10 ± 1.0 mmHg, P <0.05).

3. Cholinergic blockade had no immediate effect on intraocular pressure, and the reduction in intraocular pressure during hypoglycaemia was of similar magnitude to that observed during the control study. α-Adrenoceptor blockade did not affect basal intraocular pressure, but the small reduction induced by hypoglycaemia (from 14 ± 1.4 to 12 ± 1.1 mmHg; P = not significant) was less than the decrement observed in the control experiment. The administration of atropine or phentolamine in the absence of hypoglycaemia had no significant effect on intraocular pressure.

4. In humans the reduction of intraocular pressure induced by acute hypoglycaemia appears to be mediated principally via an α-adrenoceptor-mediated mechanism.
Measurement of whole-body protein turnover in insulin-dependent (type 1) diabetic patients during insulin withdrawal and infusion: comparison of [13C]leucine and [2H5]phenylalanine methodologies
Authors: Pacy P. J. , Thompson G. N. , Halliday D.
Published: August 2015

1. The aims of this study were twofold: (i) to investigate the ability of a recently described [2H5]phenylalanine method for quantifying whole-body protein turnover during acute physiological perturbation; (ii) to determine specifically whether the previously observed increase in protein synthesis on insulin withdrawal in insulin-dependent (type 1) diabetic patients seen when employing the [13C]leucine technique could be corroborated by using [2H5]phenylalanine.

2. Whole-body protein turnover was measured by both the [2H5]phenylalanine and [13C]leucine primed continuous infusion methods applied simultaneously to six type I post-absorptive diabetic patients during insulin withdrawal and infusion.

3. Values were determined by the [13C]leucine method by measuring either [13C]leucine (primary pool) or α-[13C]ketoisocaproic acid (reciprocal pool) enrichment in plasma.

4. Values of whole-body protein breakdown during insulin withdrawal derived from the [2H5]phenylalanine and primary and reciprocal pool [13C]leucine models respectively were 3.54 ± 0.43, 3.85 ± 0.41 and 4.62 ± 0.44 g day−1 kg−1 (means ± SD). Insulin infusion resulted in a significant reduction (P <0.02) to 3.07 ± 0.34, 3.05 ± 0.26 and 3.82 ± 0.4 g day−1 kg−1, respectively. Synthesis values fell significantly but by a smaller amount than breakdown, resulting in increased (P <0.05) net protein deposition, regardless of the model used.

5. These data demonstrate that the [2H5]phenylalanine and [13C]leucine methods generate similar results both in absolute and relative terms in response to short-term insulin infusion.

6. The confirmation of increased whole-body protein synthesis during insulin withdrawal by two independent methods supports the validity of this observation.
Serum and tissue α-l-fucosidase activity in the pre-clinical and clinical stages of hepatocellular carcinoma
Authors: Hutchinson W. L. , Johnson P. J. , Du M.-Q. , Williams R.
Published: August 2015

1. To assess the value of serum α-l-fucosidase (EC 3.2.1.51) as a marker for hepatocellular carcinoma, the activity was measured in patients with hepatocellular carcinoma and in control subjects.

2. Mean serum α-l-fucosidase activity was significantly greater in 35 patients with hepatocellular carcinoma (225 ± 69 nkat/l) than in 35 patients with cirrhosis and 20 normal subjects (134 ± 30 and 93 ± 28 nkat/l, respectively). The overlap between hepatocellular carcinoma and cirrhosis, however, was such as to severely limit any value of the enzyme as a diagnostic test.

3. In four cirrhotic patients with hepatocellular carcinoma, an increased enzyme activity was detectable in samples taken up to 66 months before the tumours were diagnosed clinically.

4. The serum activity of α-l-fucosidase fell to within the reference range after liver transplantation for hepatocellular carcinoma in three patients and in one of these a subsequent rise was associated with tumour recurrence which was diagnosed at 8 months after the rise in activity. Ineffective cytotoxic chemotherapy was also associated with a progressive rise in serum α-l-fucosidase activity.

5. α-l-fucosidase activity in tumour tissue was significantly lower than that seen in non-tumour tissue from cirrhotic patients. These reductions may represent increased transport from the tissue and may partly account for the increased serum activity found in some patients with hepatocellular carcinoma.