bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twenty-four hour C-peptide and insulin secretion rates and diurnal profiles of glucose, lipids and intermediary metabolites in cirrhosis
Authors: Kruszynska Yolanta T. , Munro Janet , Home Philip D. , McIntyre Neil 
Published: August 2015

1. To examine the contributions of hypersecretion and decreased insulin clearance to the hyperinsulinaemia of cirrhosis, insulin secretion was calculated over the day from serum C-peptide concentrations and C-peptide metabolic clearance rate. The latter was measured during infusions of recombinant human C-peptide. In cirrhotic patients (n = 9) insulin secretion rate was twice that of normal control subjects (n = 10), both in the basal state [02.00–07.00 hours, 15.7 ± 2.1 (mean ± sem) nmol/h (2.6 ± 0.4 units/h) versus 7.0 ± 0.9 nmol/h (1.2 ± 0.2 units/h), P&lt;0.002] and over 24 h [787 ± 93 nmol (132 ± 16 units) versus 346 ± 34 nmol (58 ± 6 units), P&lt;0.001]. However, the area under the serum insulin concentration curve was approximately six times greater in the cirrhotic patients (24 h basal, 6.3 ± 1.0 versus 1.1 ± 0.31 nmol l−1 h, P&lt;0.001; 24 h total, 21.7 ± 3.2 versus 3.7 ± 0.7 nmol l−1 h, P&lt;0.001). Thus, despite impairment of insulin clearance there is continuing hyper-section of insulin in cirrhosis.
2. The relationship of carbohydrate and lipid metabolism with insulin secretion was assessed. In cirrhotic patients, 24 h blood glucose profiles showed a worsening of glucose tolerance over breakfast, despite greater insulin secretion compared with other meals, suggesting that the insulin insensitivity of cirrhosis is worse at this time.
3. Cirrhotic patients showed impaired suppression of blood glycerol levels after meals but normal suppression of serum non-esterified fatty acid concentrations. The greatest differences in the profiles of serum lipids and lipid-related metabolites in cirrhotic patients and control subjects occurred at night. Whereas in control subjects, serum non-esterified fatty acid, blood glycerol and blood 3-hydroxybutyrate concentrations peaked between 01.00 and 03.00 hours, falling gradually thereafter until 08.00 hours, in cirrhotic patients serum non-esterified fatty acid and blood glycerol levels showed a gradual increase during the night to reach maximal levels at 08.00 hours when they were twice those of control subjects (P&lt;0.001).
4. The blood 3-hydroxybutyrate and serum triacyl-glycerol profiles suggested that in cirrhotic patients there was preferential utilization of non-esterified fatty acids for ketogenesis and reduced re-esterification to triacylglycerol.
Colonic absorption of human calcitonin in man
Authors: Antonin K. H. , Saano V. , Bieck P. , Hastewell J. , Fox R. , Lowe P. , MacKay M. 
Published: August 2015

1. Human calcitonin was administered into the distal colon and by intravenous infusion in eight healthy subjects in an open, fixed sequence, cross-over bioavailability study.
2. Intravenously infused human calcitonin elicited a standard pharmacokinetic profile in eight healthy subjects with a biphasic elimination with half-lives of 10.2 ± 0.7 min and 37.8 ± 2.5 min.
3. Colonoscopically administered human calcitonin was absorbed across the distal colonic mucosa in low amounts with a bioavailability of 0.00–0.22%.
4. Absorption from the distal colon was impeded by the presence of faecal material in three of the eight subjects.
5. We conclude that human calcitonin crosses the gastrointestinal epithelium of man. This may demonstrate the feasibility of an oral form for clinical use.
α-Tocopherol, lipids and lipoproteins in knee-joint synovial fluid and serum from patients with inflammatory joint disease
Authors: Fairburn K. , Grootveld M. , Ward R. J. , Abiuka C. , Kus M. , Williams R. B. , Winyard P. G. , Blake D. R. 
Published: August 2015

1. We have determined the antioxidant status of synovial fluid and serum of patients with inflammatory joint disease in terms of the biologically active lipid-soluble antioxidant, α-tocopherol. Synovial fluid concentrations of α-tocopherol were significantly lower relative to those of paired serum samples (P&lt;0.001). Serum levels of α-tocopherol in these patients did not differ significantly from those in control serum.
2. Lower concentrations of cholesterol, triacylglycerol and low-density lipoprotein were also observed in patients' synovial fluid compared with matched serum samples. However, multiple regression analysis of the data indicated that there remained a significant depletion of α-tocopherol, which was largely independent of these co-variables, in inflammatory synovial fluid. These findings are consistent with the consumption of α-tocopherol within the inflamed joint via its role in terminating the process of lipid peroxidation.
3. Nuclear magnetic resonance spectroscopic analysis of matched inflammatory synovial fluid and serum confirmed lower concentrations of triacylglycerol in synovial fluid together with evidence of a shortened mean triacylglycerol chain length. The latter metabolic difference suggests an increased utilization of triacylglycerols for energy within the inflamed joint.
Effects of parathyroid hormone and calcium and their interrelationship on urinary acidification in the rat
Authors: Gil F. Zaladek , Silva V. L. Costa , Cavanal M. F. , Malnic G. 
Published: August 2015

1. The influence of thyroparathyroidectomy on renal function and specifically on acid excretion was studied in rats with or without oral supplementation of calcium.
2. Thyroparathyroidectomy caused a significant decrease in glomerular filtration rate, in the urinary/ plasma inulin ratio and in overall acid excretion. These changes were not corrected by calcium supplementation.
3. Rates of proximal tubular acidification were studied by means of double-barrelled resin/reference microelectrodes. Acidification half-time was significantly increased in both thyroparathyroidectomized and calcium-supplemented thyroparathyroidectomized rats (838 s and 7.40 s, respectively) compared with control rats (5.44 s).
4. When 10−6 mol/l A23187, a calcium ionophore, was added to the luminal bicarbonate solution, the acidification half-time returned to 3.97 s in the thyroparathyroidectomized rats, whereas no significant changes were detected in the properties of acidification in the control rats.
5. These data show that parathyroid hormone and cellular calcium are important factors involved in proximal tubular H+ secretion, which appears to be largely dependent on a well-defined concentration range of these agents.
Aortic compliance in young patients with heterozygous familial hypercholesterolaemia
Authors: Lehmann E. D. , Watts G. F. , Fatemi-Langroudi B. , Gosling R. G. 
Published: August 2015

1. Aortic compliance and plasma lipid and lipoprotein levels were measured in 20 young patients with heterozygous familial hypercholesterolaemia and in 20 age- and sex-matched control subjects.
2. Patients with familial hypercholesterolaemia had significantly higher plasma cholesterol, low-density lipoprotein-cholesterol and triacylglycerol levels than control subjects (P&lt;0.001, P&lt;0.001 and P&lt;0.005, respectively). The patients with familial hypercholesterolaemia also had significantly more compliant (distensible) aortas than the control subjects (P&lt;0.001), a significant inverse correlation being observed between compliance and age (r = −0.73, P&lt;0.001) and between compliance and mean blood pressure (r = −0.60, P&lt;0.005).
3. When the effects of age and sex on aortic compliance were corrected for, the blood pressure effect disappeared, significant correlations being observed between normalized compliance and cholesterol (r = 0.50, P&lt;0.03), low-density lipoprotein-cholesterol (r = 0.54, P&lt;0.01), high-density lipoprotein-cholesterol (r = −0.44, P&lt;0.05), low-density lipoprotein-/high-density lipoprotein-cholesterol ratio (r = 0.60, P&lt;0.006) and duration of disease (r = 0.67, P&lt;0.002). Multivariate regression analysis showed that the low-density lipoprotein-/high-density lipoprotein-cholesterol ratio (P&lt;0.03) and duration of disease (P&lt;0.04) were the best predictors of normalized compliance.
4. We suggest that the measurement of aortic compliance in young patients with familial hypercholesterolaemia may potentially be a useful, noninvasive, research tool for assessing their susceptibility to atheroma.
Effect of aseptic abscesses in protein-deficient rats on the relationship between interleukin-6 and the acute-phase protein, α2-macroglobulin
Authors: Jennings G. , Cruickshank A. M. , Shenkin A. , Wight D. G. , Elia M. 
Published: August 2015

1. Rats established on a normal (20% protein) diet or a protein-deficient (3% protein) diet were given either a subcutaneous injection of turpentine (5 ml/kg), which induces formation of aseptic abscesses, or saline. Plasma samples were obtained at timed intervals (0–14 days) after the injection for determination of albumin, total protein, α2-macroglobulin (a major acute-phase protein in the rat) and interleukin-6 concentrations. The magnitude and pattern of the acute-phase protein response was then compared with the local inflammatory reaction, assessed histologically, and with changes in the circulating concentration of interleukin-6, which is an important mediator of the acute-phase protein response.
2. After turpentine injection there was an early fall in the plasma albumin and total protein concentrations in both normal and protein-deficient rats. After 12 h the total protein concentration increased in both groups of animals reaching a peak at about 48 h, whereas the plasma albumin concentration continued to fall reaching a minimum at 48 h. The main α2-macroglobulin response was delayed and attenuated in the protein-deficient rats (onset 9 versus 24 h, peak concentration 8.95 ± 0.5 versus 5.33 ± 0.75 g/l, P&lt;0.01, and area under the concentration-time curve 18.43 ± 2.13 versus 7.96 ± 1.48 gl−1 days, P&lt;0.01, in the normal group and protein-deficient group, respectively).
3. The circulating interleukin-6 concentration showed a transient early rise at 1 h, and was followed by a larger more sustained peak at 6–48 h. The onset of the secondary rise preceded the onset of the α2-macroglobulin response in both groups of animals, but both the onset and rate of rise were slower in the protein-deficient animals. The peak concentration of interleukin-6 and the area under the concentration-time curve were not significantly different between the groups. There were also no obvious differences in the intensity of the local inflammatory reaction, although the onset of repair was delayed in the protein-deficient animals.
4. This study confirms that the acute-phase protein response is attenuated by protein deficiency, but this does not appear to be due to an attenuated local inflammatory response after turpentine injection. The delayed onset of the interleukin-6 response may explain the delayed onset of the acute-phase response, but the overall magnitude of the interleukin-6 response (total area under the concentration-time curve), which was similar in the two groups, does not explain the overall attenuation of the α2-macroglobulin response.
Biochemical characteristics of human renin expressed in transgenic mice
Authors: Takaori Kazuo , Kim Shokei , Fukamizu Akiyoshi , Sagara Masashi , Hosoi Masayuki , Katsuki Motoya , Murakami Kazuo , Yamamoto Kenjiro 
Published: August 2015

1. Biochemical properties of human renin expressed in transgenic mice (hRN8-12 mice) carrying the human renin gene (Fukamizu et al. Biochem Biophys Res Commun 1989; 165: 826–32) were examined. The optimum pH of the enzymic activity against human angiotensinogen was 5.5 for both plasma and renal human renin in the hRN8-12 mice. Plasma concentrations of human active and inactive renin in the plasma of hRN8-12 mice were 16.7 ± 2.8 and 79.9 ± 14.0 pmol of angiotensin 1 h−1 ml−1, respectively, thereby indicating that the predominant form of plasma human renin is the inactive form, as is the case in humans.
2. The molecular masses of plasma human active and inactive renin and renal human active renin in the hRN8-12 mice were estimated to be 46kDa, 48kDa and 44kDa, respectively, as determined by h.p.l.c. on G3,000SW.
3. Human renin in the hRN8-12 mouse kidney was bound to a concanavalin A-Sepharose column, and was eluted with α-methyl-d-mannoside, showing that this renin is glycosylated, as is native human renin.
4. Low sodium treatment of the hRN8-12 mice for 2 weeks increased plasma human active renin, renal human renin and renal human renin mRNA levels by 2.6-, 3.8- and 2.8-fold, respectively. Thus, the biosynthesis and secretion of renal human renin in these transgenic mice are obviously stimulated by sodium depletion.
Renal and systemic sympathetic counterregulation in response to vasodilators in renovascular hypertension
Authors: Herlitz Hans , Hjemdahl Paul , Volkmann Reinhard , Jensen Gert , Aurell Mattias 
Published: August 2015

1. Twenty-two patients with renovascular hypertension and significant lateralization of renin secretion were investigated with respect to arterial and renal venous plasma noradrenaline and dopamine concentrations before and 30 min after two different blood pressure-lowering procedures (enalaprilat or dihydralazine intravenously).
2. In one group of patients (n = 10) blood pressure reduction by 7.5 mg of dihydralazine caused stimulation of the renin-angiotensin system and increased heart rate (P &lt; 0.01) as well as arterial and renal venous plasma noradrenaline and dopamine concentrations (P &lt; 0.01 for both). The elevation of the plasma dopamine concentration was more pronounced than that of noradrenaline, yielding increased dopamine/noradrenaline ratios both peripherally (P &lt; 0.05) and in the renal veins (P &lt; 0.05).
3. In the second group of patients (n = 12) a comparable reduction in blood pressure elicited by 1.25 mg of enalaprilat was not accompanied by alterations in heart rate or in noradrenaline or dopamine levels in arterial plasma or renal venous plasma from either kidney.
4. Thus, inhibition of angiotensin-converting enzyme does not elicit the expected sympathetic counter-regulatory response to blood pressure reduction; the mechanism(s) involved remains to be clarified.
Effect of inflammation on peripheral airway reactivity in dogs
Authors: Cormier Y. , Whittom R. , Boulet L. P. , Sériès F. 
Published: August 2015

1. Eight mongrel dogs were studied to evaluate the effect of local inflammation on the response of collateral airways to histamine. In each dog we measured the baseline collateral resistance and its response to increasing doses of nebulized histamine. These measurements were obtained at weekly intervals, twice under control conditions and in three subsequent weeks after a local instillation of the bacteria Bordetella bronchiseptica. On each study day, after the measurements of collateral resistance, we lavaged the studied lung segment by instilling and aspirating 100 ml of saline (four 25 ml aliquots). All studies were performed in the same lung segment.
2. Collateral resistance remained stable under control conditions at 19.5 ± 7.2 and 11.7 ± 32 cm H2OI−l mm. With a bacteria-induced, mostly neutrophilic, inflammation, collateral resistance initially increased to 70.2 ± 18.6 cm H2OI−1 min after 1 week and subsequently decreased towards control values (47.3 ± 13 and 30.7 ± 10.1 cm H2OI−1 min at 21 and 29 days, respectively). Collateral pathways reactivity, expressed as the slope of the relationship collateral resistance/log (1 + [histamine]), remained unchanged throughout the study. The values of this slope were (mean ± SEM) 0.021 ± 0.003 and 0.022 ± 0.004 in the two control studies and 0.025 ± 0.004, 0.030 ± 0.006 and 0.023 ± 0.003 in the three subsequent weekly studies. Inflammation, evaluated by the number of bronchoalveolar lavage cells and the percentage of neutrophils in bronchoalveolar cells, closely paralleled baseline collateral resistance with a peak value at the first week after the infection.
3. Local inflammation increases collateral resistance by its mechanical effects, and does not modify the responsiveness of collateral pathways to nebulized histamine.
Intracellular pH regulation in isolated myocytes from adult rat heart in HCO-3-containing and HCO-3-free media
Authors: Ng L. L. , Davies J. E. , Quinn P. 
Published: August 2015

1. Using microfluorimetry, intracellular pH, buffering capacity and intracellular pH recovery from intracellular acidosis were determined in isolated adult rat ventricular myocytes, in buffers with and without HCO-3.
2. In nominally HCO-3-free media, the intracellular pH was higher than in HCO-3-containing media. Buffering capacity at resting intracellular pH and at a pH of about 6.3 was also lower in HCO-3-free media.
3. In HCO-3-free media, recovery from an acid load after an NH4C1 prepulse was almost completely inhibited by the Na+/H+ antiport activity specific inhibitor ethylisopropyl amiloride. However, in the presence of HCO-3, H+ efflux rate was enhanced, and ethylisopropyl amiloride led to only partial inhibition of H+ efflux. Complete inhibition was achieved only with further addition of the anion-transport inhibitor 4,4′-di-isothiocyanatostilbene-2,2′-disulphonate.
4. Thus, in adult rat ventricular myocytes, recovery from intracellular acidosis in the absence of HCO-3 was almost wholly due to Na+/H+ antiport activity. In the more physiological situation with HCO-3 present, a third of the recovery from an intracellular acid load was attributed to an additional external Na+-dependent di-isothiocyanatostilbene-disulphonate-sensitive H+ efflux.
A novel thiadiazinone derivative fully reverses acidosis-induced depression of force in cardiac muscle by a calcium-sensitizing effect
Authors: Lee J. A. , Shah N. , White J. , Orchard C. H. 
Published: August 2015

1. We examined the effects of the novel thiadiazinone derivative EMD 57033 on developed force and intracellular [Ca2+] in cardiac muscle during control conditions (pH 7.35) and in acidosis (pH 6.8).
2. In the control solution, application of EMD 57033 fully activated the muscle. Acidosis reduced developed force to 18% of maximum, but application of EMD 57033 in acid solution was able to fully reverse this effect and restore force to its previous maximum.
3. During the positive inotropic effect in acidosis, the Ca2+ transients declined to 62% of their initial amplitude, whereas force increased to 557%.
4. These observations suggest that EMD 57033 increases force by a Ca2+-sensitizing action in intact cardiac muscle. Since EMD 57033 is able to fully reverse the effects of acidosis on force without increasing the amplitude of the Ca2+ transients, this compound and others with similar mechanisms of action appear to hold particular promise for heart failure therapy.
Progressive deterioration of muscles in mdx mice induced by overload
Authors: Dick J. , Vrbová G. 
Published: August 2015

1. Extensor digitorum longus muscles of C57 BL/10 and mdx mice were overloaded by removing the synergist tibialis anterior muscle of 9–12-day-old animals. The effect of this operation on the weight, contractile properties and force of the extensor digitorum longus muscle was examined at two different ages, i.e. at 2–3 months (young group) and at 5–8 months (old group). The changes with age in both the control and overloaded muscles of normal and mdx mice are also described. The values obtained from the overloaded muscles were always compared with those for the control, unoperated extensor digitorum longus.
2. In the normal strain of mice the weight of the overloaded extensor digitorum longus muscle in the younger group was increased and it remained higher in the older animals. In the mdx mice the overloaded extensor digitorum longus muscles weighed more in the younger animals but not in the older group of mice.
3. The twitch and tetanic tensions of the overloaded muscles were slightly, but not significantly, increased in the younger group of mdx mice, whereas in the older animals there was a significant decrease in both twitch and tetanic tensions.
4. Thus the overloaded muscles from mdx mice progressively deteriorated with age. In both strains of mice the overloaded muscles become less fatiguable with time.
Thyroid hormone stimulates release of calmodulin-enhancing activity from human erythrocyte membranes in vitro
Authors: Lawrence William D. , Deziel Mark R. , Davis Paul J. , Schoenl Marion , Davis Faith B. , Blas Susan D. 
Published: August 2015

1. Thyroid hormone (L-thyroxine, 10−10mol/l) incubated in vitro with human erythrocyte membranes induced the release of a soluble calmodulin-like material, the 3′:5′-cyclic nucleotide phosphodiesterase-stimulating activity of which was at least six-fold greater than its concentration measured by a specific calmodulin radioimmunoassay.
2. The material had the characteristics of calmodulin in that it stimulated both phosphodiesterase and erythrocyte Ca2+-ATPase activities, cross-reacted with and was neutralized by anti-calmodulin antibody, was adsorbed by phenothiazine-Sepharose and was heat-stable. Control supernatant from the incubation of membranes in the absence of thyroxine contained calmodulin, the bioactivity of which was not enhanced beyond that predicted from radioimmunoassay. Subsequent addition of thyroxine did not increase calmodulin bioactivity. Calmodulin-agarose removed calmodulin-enhancing activity from the supernatant.
3. Thus, the enhancing factor(s) appears to interact directly with calmodulin. These observations indicate that thyroid hormone promotes the release from human erythrocyte membranes of a soluble factor (or factors) which binds to calmodulin and significantly increases its bioactivity. This enhancing activity is similar to that of a calmodulin activator described in a rat model of hypertension (S.-L. Huang et al., J Clin Invest 1988; 82: 276-81).
Uromodulin levels are decreased in urine during acute tubular necrosis but not during immune rejection after renal transplantation
Authors: McLaughlin P. Jeremy , Alkawa Atsushi , Davies Helen M. , Ward Richard G. , Bakran Ali , Sells Robert A. , Johnson Peter M. 
Published: August 2015

1. Uromodulin, an immunosuppressive glycoprotein found in urine, is a high-affinity binding ligand for certain cytokines, including tumour necrosis factor.
2. Its occurrence in urine was monitored after renal transplantation to investigate whether this simple urine test might differentiate common early causes of graft failure: acute immune rejection and acute tubular necrosis.
3. Diluted urine was assayed for uromodulin using a sandwich enzyme-linked immunosorbent assay. When graft function failed due to acute tubular necrosis, urinary uromodulin levels were significantly depressed compared with levels in urine produced during biopsy-proven acute immune rejection episodes (P &lt; 0.01) or during periods of stable graft function (P &lt; 0.02). This suggests that urinary levels of uromodulin may reflect tubular damage rather than other causes of graft functional failure.
4. The cytokine tumour necrosis factor, which binds with high affinity to uromodulin, was found in 30% of urine samples in association with immune rejection episodes, but not during acute tubular necrosis. However, the presence of urinary tumour necrosis factor was not related to levels of uromodulin in the same sample.