bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pineal Hyperactivity in Spontaneously Hypertensive Rats: Muscarinic Regulation of Indole Metabolism
Authors: Finocchiaro Liliana M. E. , Scheucher Angelika , Alvarez Azucena L. , Finkielman Samuel , Nahmod Victor E. , Pirola Carlos J. 
Published: August 2015

1. Choline acetyltransferase activity and [3H]quinuclidinyl benzylate-binding sites were detected in the pineal gland of normotensive Wistar—Kyoto rats and of spontaneously hypertensive rats.
2. In vitro, muscarinic activation by pilocarpine increased the pineal metabolic production of hydroxyindole derivatives up to 5-hydroxytryptamine and produced a less marked stimulation of melatonin biosynthesis.
3. Electrical field stimulation of pineal gland slices caused similar metabolic effects.
4. Muscarinic blockade with atropine inhibited the effects on hydroxyindole metabolism.
5. [3H]Quinuclidinyl benzylate-binding sites, indicative of muscarinic receptors, were more numerous, and basal 5-hydroxytryptamine and melatonin levels were higher, in the pineal gland of spontaneously hypertensive rats compared with Wistar—Kyoto rats.
6. The atropine-sensitive metabolic effects of pilocarpine and electrical field stimulation on the pineal gland were increased in spontaneously hypertensive rats compared with Wistar-Kyoto rats.
Insulin Resistance after Surgery: Normalization by Insulin Treatment
Authors: Brandi L. S. , Frediani M. , Oleggini M. , Mosca F. , Cerri M. , Boni C. , Pecori N. , Buzzigoli G. , Ferrannini E. 
Published: August 2015

1. Injury is known to be associated with variable degrees of tissue insensitivity to insulin. We measured insulin resistance in a group of non-obese, glucose-tolerant patients undergoing major elective surgery with an uncomplicated post-operative course.
2. Shortly after surgery, hyperglycaemia (7.3 ±0.6 versus 4.2 ± 0.3 mmol/l glucose pre-surgery, mean ± sem, P &lt; 0.01) with normal insulin concentrations (73 ±15 versus 64 ± 18 pmol/l) suggested the presence of insulin resistance. Counter-regulatory hormones were raised, whole-body protein oxidation was doubled (P &lt; 0.01) and energy expenditure was up by 18% (P &lt; 0.01).
3. Insulin sensitivity was quantified by clamping plasma glucose concentrations at 5.6 mmol/l during 24 h of total parenteral nutrition (15% protein, 55% glucose and 30% fat, supplying 1.25 times the measured resting energy expenditure) with a variable infusion of exogenous insulin. After surgery, eight times more insulin was needed than before surgery (14.14±1.15 versus 1.78±0.29 pmol min−1 kg−1, P &lt; 0.001) to maintain euglycaemia.
4. After surgery, stimulation of net carbohydrate oxidation (18.8 ±1.4 versus 17.2 ± 1.8μmol min−1 kg−1 pre-operatively, not significant), suppression of lipolysis and lipid oxidation and inhibition of ketogenesis occurred to the same extent as before surgery. Of the infused nutrients, the glucose was all oxidized, amino acids replaced endogenous protein losses (= neutral nitrogen balance) and lipids were stored. Insulin administration caused no further increment in oxygen consumption or energy expenditure.
5. We conclude that: (a) uncomplicated surgery causes severe insulin resistance, the effects of which insulin can reverse; and (b) with an energy supply only slightly in excess of demand, insulin supplementation preserves body protein and energy stores effectively.
Generation of the Membrane Attack Complex during Haemodialysis: Impact of Classical and Alternative Pathway Components
Authors: Hauser Anna-Christine , Derfler Kurt , Stockenhuber Felix , Janata Oskar , Balcke Peter 
Published: August 2015

1. The generation of the plasma SC5b—9 complex (the soluble form of the membrane attack complex) during haemodialysis was studied in 29 patients together with markers of the classical (C4d fragment) and alternative (Bb fragment) pathways and the common iC3b fragment.
2. In the patients dialysed with Hemophan and Cuprophan membranes, a rapid increase in the plasma levels of SC5b—9 complex, Bb fragment and iC3b fragment occurred within 15 min of the initiation of the haemodialysis procedure. The SC5b—9 complex and the Bb fragment concentrations remained at a plateau until 120 min thereafter. The iC3b fragment level showed a continual decline.
3. The C4d fragment concentrations remained unchanged, indicating that generation of the membrane attack complex is most likely due only to activation of the alternative pathway.
4. The generation of the membrane attack complex occurred throughout the full haemodialysis period. In patients treated with Polysulfon membranes no statistically significant variation in these components was noted.
5. The study shows that the membrane attack complex may be generated during the full period of the haemodialysis session and is a stable index of biocompatibility.
6. Moreover, it seems be involved directly in haemodialysis-associated phenomena.
Aldose Reductase Messenger RNA in the Lens Epithelium in vivo: Effects of Diabetes Mellitus and Galactosaemia
Authors: Lightman Susan , Bondy Carolyn , Lightman Stafford , Kador Peter 
Published: August 2015

1. Quantitative in situ hybridization histochemistry was used to examine the regulation of aldose reductase messenger RNA in the rat lens after the induction of diabetes mellitus or after feeding a 50% (w/w) galactose diet.
2. Although increased staining for aldose reductase in the lens epithelium has previously been observed by immunohistochemistry after 3 weeks of diabetes or after 7 days of galactose feeding, we have not been able to detect any increase in the amount of aldose reductase messenger RNA in these cells as compared with controls (113 ± 7%, 105 ± 9%, 100 ±7%, respectively) at these time points (P &gt;0.05).
3. After 15 days of galactose feeding, however, there was a significant increase of 140% (± 12%) in the amount of aldose reductase messenger RNA in the lens epithelial cells as compared with controls (P = &lt; 0.001).
4. These results demonstrate that increased availability of galactose, a high-affinity substrate for the enzyme, leads to increased aldose reductase messenger RNA, which suggests a role for aldose reductase in sugar metabolism in the lens.
Relationship between the Maximum Velocity and Sodium Affinity of the Erythrocyte Sodium Pump and its Rate Constant in Blood
Authors: Thomas T. H. , MacPhail S. , Mott V. , Wilkinson R. 
Published: August 2015

1. Young and mature erythrocytes from 15 normal subjects were used to compare the sodium pump rate constant measured in whole blood with the more definitive sodium affinity constant and maximum velocity of the sodium pump measured in artificial media using sodium-loaded cells.
2. Similar values were obtained from both erythrocyte fractions for the sodium affinity constant and maximum velocity and also by using two different plots. The median error in the estimate of individual sodium affinity constants and maximum velocities from regression analysis was about 20% and the precision was not improved by combining the data points for the two erythrocyte fractions.
3. The rate constant in whole blood was closely related to the sodium affinity constant and maximum velocity of the sodium pump (r = 0.75), suggesting that it was a reasonable overall assessment of available sodium pump activity.
4. Differences in the rate constant between subjects were due to differences in both the maximum velocity and sodium affinity constant of the sodium pump so that the rate constant could not be used as a guide to the underlying sodium pump physiology.
Dose-response relationships for the effects of insulin on glucose and fat metabolism in injured patients and control subjects
Authors: Henderson Alistair A. , Frayn Keith N. , Galasko Charles S. B. , Little Roderick A. 
Published: August 2015

1. Twenty-four patients were studied at around 7 days after musculoskeletal injuries in order to define the nature of the impairment of sensitivity to insulin. Insulin was infused at 6, 35, 200 or 1200 m-units min−1 m−2 for 2 h and the plasma glucose concentration was ‘clamped’ at 5 mmol/l. Forearm (uninjured) glucose extraction and blood flow were measured, and whole-body substrate oxidation and energy production rates were assessed by indirect calorimetry. The patients were compared with normal control subjects.
2. Plasma insulin concentrations during infusion were similar in patients and control subjects, showing a similar metabolic clearance of insulin. At each infusion rate, the rate of glucose infusion needed to maintain euglycaemia was less in the patients than in the control subjects. The dose-response curve for whole-body glucose infusion rate against plasma insulin concentration showed diminished sensitivity and diminished maximal response in the patients. A similar pattern was seen for forearm glucose uptake, with a marked impairment of both sensitivity to insulin and maximal responsiveness.
3. The resting metabolic rate was increased in the patients compared with the control subjects, but failed to respond to insulin infusion, so that final metabolic rates were similar in patients and control subjects. At the higher insulin infusion rates, the final rate of whole-body oxidation of carbohydrate was significantly less in the patients than in the control subjects, and that of fat was significantly greater.
4. The hormonal background to this picture of insulin resistance was not striking: the injured patients showed small elevations in plasma cortisol, glucagon and noradrenaline concentrations, but not in plasma adrenaline concentration.
5. It is concluded that the insulin resistance after injury reflects both diminished responsiveness and diminished sensitivity, affects both fat and carbohydrate metabolism, and must be explained by factors other than the usually considered ‘counter-regulatory’ hormones.
Effects of dichloroacetate and bicarbonate on haemodynamic parameters in healthy volunteers
Authors: Ludvik B. , Peer G. , Berzlanovich A. , Stifter S. , Graf H. 
Published: August 2015

1. It has been shown that sodium bicarbonate has no effect or could even be detrimental in various forms of metabolic acidosis. Dichloroacetate, a stimulator of the pyruvate dehydrogenase complex, might offer an alternative treatment. The present study therefore examines the metabolic and haemodynamic effects of dichloroacetate and sodium bicarbonate in healthy volunteers.
2. On 2 different days, sodium dichloroacetate (50 mg/kg body weight) or sodium bicarbonate (1.5 mmol/kg body weight) was given intravenously as as single bolus in 10 healthy volunteers. Haemodynamic parameters were measured using a microprocessor-controlled system. Measurements were performed before and 30 and 60 min after infusion.
3. After administration of dichloroacetate, cardiac index increased from 2.3 ± 0.03 to 2.7 ± 0.1 1 min−1 m−2 (P &lt;0.05), peripheral vascular resistance decreased from 266 ± 9.7 to 240 ± 1.7 kPa s l−1 (2662 ± 97 to 2398 ± 169 dyn s cm−5, P &lt;0.05), oxygen availability increased from 442 ± 16 to 535 ± 30 ml min−1 m−2 (P &lt;0.05) and serum lactate concentration fell from 1.4 ± 0.14 to 0.6 ± 0.1 mmol/l (P &lt;0.05). With infusion of sodium bicarbonate there were no significant effects on any of these variables.
4. Our results show that dichloroacetate administered intravenously reduces the serum lactate concentration. The main effects of dichloroacetate itself are on the haemodynamic variables. Dichloroacetate increases cardiac index and oxygen availability and decreases peripheral vascular resistance, whereas sodium bicarbonate has no effect on haemodynamic or metabolic parameters. These data give some further insights in the actions of dichloroacetate and support the use of dichloroacetate as alternative therapy in various forms of metabolic acidosis.
Lymphocytotoxins in sera from highly sensitized multiparous dialysis patients: antibody class, relationship with the HLA and with paternal antigens
Authors: Propper D. J. , Leheny W. A. , Urbaniak S. J. , Catto G. R. D. , MacLeod A. M. 
Published: August 2015

1. Sera from 11 highly sensitized multiparous dialysis patients were studied in order to define the target antigens, antibody class and relationship with paternal HLA class I antigens of the underlying lymphocytotoxic antibodies. All sera contained lymphocytotoxic antibodies to over 70% of a panel of lymphocytes from 24 donors (panel reactivity &gt; 70%).
2. Inhibition of cytotoxic activity against paternal lymphocytes by monoclonal antibodies to HLA framework determinants indicated that all 11 sera contained lymphocytotoxic antibodies to paternal class I antigens. In addition, five sera contained lymphocytotoxic antibodies to paternal class II antigens.
3. In order to determine the extent to which lymphocytotoxic antibodies were directed to paternal antigens, the panel reactivity of sera was compared before and after absorption with paternal peripheral blood lymphocytes. Over 50% of panel reactivity was absorbed from eight out of 11 sera, and in three of these 11 over 80% was absorbed. In the majority of patients this change in panel reactivity could be ascribed to binding of lymphocytotoxic antibodies to specific paternal class I antigens.
4. Digestion of sera with dithiothreitol had no significant effect on panel reactivity, indicating that the lymphocytotoxic antibodies were of immunoglobulin G class.
5. No sera reacted with either autologous lymphocytes or K562 cells, indicating an absence of autoantibodies.
6. These studies imply that panel-reactive lymphocytotoxic antibodies in the sera of highly sensitized multiparous patients are those which mediate hyperacute renal allograft rejection. Their development may be related to secondary humoral responses to angtigens in blood transfusions from donors who share paternal class I specificities.
Differential effects of atrial natriuretic peptide and dopamine on urinary protein excretion in chronic glomerulonephritis
Authors: Hirata Yasunobu , Ishii Masao , Fukui Kazushige , Hayakawa Hiroshi , Suzuki Etsu , Sugimoto Tokuichiro , Kimura Kenjiro , Matsuoka Hiroaki , Sugimoto Tsuneaki 
Published: August 2015

1. To examine whether or not atrial natriuretic peptide-induced proteinuria simply results from increases in urine flow or glomerular filtration rate, we infused dopamine (1 μg min−1 kg−1) and α-human atrial natriuretic peptide (0.025 μg min−1 kg−1) into nine patients with chronic glomerulonephritis and nine essential hypertensive patients without renal damage, and compared the effects of the two agents on renal function and urinary protein excretion.
2. In patients with chronic glomerulonephritis, dopamine infusion significantly increased urinary sodium excretion (+ 59%), renal blood flow (+ 20%) and creatinine clearance (+ 14%). However, urinary protein excretion was not changed. Addition of atrial natriuretic peptide to the dopamine infusion further increased urinary sodium excretion and maintained creatinine clearance at the same level. In contrast to the infusion of dopamine alone, atrial natriuretic peptide markedly increased urinary protein excretion (77 versus 229 mg min−1 m2, P &lt; 0.02). Furthermore, the addition of atrial natriuretic peptide elevated the urinary protein/creatinine ratio (1.55 versus 5.35, P &lt; 0.05), while dopamine alone did not(1.55 versus 1.45, not significant).
3. In essential hypertensive patients, dopamine and dopamine plus ANP showed renal effects similar to those of chronic glomerulonephritis; however, the urinary excretion of protein was not changed significantly.
4. These results suggest that atrial natriuretic peptide may increase urinary protein excretion mainly by increasing the permeability of the damaged glomeruli to protein rather than by simply increasing urine flow or glomerular filtration. Possible mechanisms underlying the proteinuria-increasing effects of atrial natriuretic peptide are discussed.
Fasting Plasma Glucose Levels and Endogenous Androgens in Non-Diabetic Postmenopausal Women
Authors: Khaw Kay-Tee , Barrett-Connor Elizabeth 
Published: August 2015

1. The clinical association between glucose intolerance, hyperinsulinaemia, insulin resistance and hyperandrogenism is well recognized in premenopausal women with polycystic ovarian disease. We examined the hypothesis that fasting plasma glucose levels might be related to endogenous androgen levels in postmenopausal women in the absence of overt clinical disease.
2. In a Southern Californian cohort of 848 non-diabetic postmenopausal women aged 50–79 years, fasting plasma glucose levels positively correlated with levels of the endogenous androgens dehydroepiandrosterone sulphate and free testosterone and negatively with sex-hormone-binding globulin across the whole range of glucose and hormone levels. Mean dihydroepiandro-sterone sulphate and free testosterone levels were 16% and 46% higher, respectively, and mean sex-hormone-binding globulin levels 27% lower in the top compared with the bottom quartile of fasting plasma glucose levels. This relationship was independent of age, body mass index, cigarette smoking habit and exogenous oestrogen use.
3. These findings raise questions about the possible physiological role of androgens in the regulation of glucose metabolism and insulin resistance and, possibly, in the mediation of the some of the cardiovascular consequences of diabetes in women.
Hepatic Phosphofructokinase-1 Activity and Fructose 2,6-Bisphosphate Levels in Patients with Abdominal Sepsis
Authors: Arnold Jeff , Hamer Marcus J. , Irving Miles 
Published: August 2015

1. In sepsis various processes of carbohydrate metabolism, such as hepatic gluconeogenesis and glycolysis, are altered. Phosphofructokinase-1, a key glycolytic enzyme, is controlled in the long term via regulation of synthesis and degradation of the protein itself, while in the short term it is regulated by allosteric effectors, such as fructose 2,6-bisphosphate (the most potent). In the present study hepatic phosphofructokinase-1 activity as well as phosphofructokinase-2 activity and the concentration of fructose 2,6-bisphosphate were assayed to determine if they might contribute to the derangement of carbohydrate metabolism seen commonly in sepsis.
2. The levels of glycogen and fructose 2,6-bisphosphate and the activity of phosphofructokinase-1 and phosphofructokinase-2 were determined in hepatic biopsies obtained at laparotomy from six patients with and seven patients without abdominal septic foci.
3. A significant increase in plasma lactate concentration was observed in the septic patients, whereas no significant differences in tissue glycogen content or plasma glucose concentration were seen between the groups.
4. No significant change in plasma insulin concentration was observed. However, levels of the counter-regulatory hormones (glucagon, cortisol and adrenaline) were elevated in the septic patients.
5. A 60% decrease in hepatic phosphofructokinase-1 activity was seen in the septic patients. However, no significant changes in hepatic phosphofructokinase-2 activity and fructose 2,6-bisphosphate content were observed in the septic patients.
6. The present results demonstrate that the decrease in hepatic phosphofructokinase-1 activity occurring in sepsis does not appear to reflect alterations in the concentration of fructose 2,6-bisphosphate.
Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis
Authors: Williams Bryan , Layward Ellis , Walls John 
Published: August 2015

1. Chronic metabolic acidosis is associated with impaired growth and negative nitrogen balance, suggesting that it promotes endogenous protein catabolism.
2. Skeletal muscle is the major repository of body protein and is a potential target for stimuli of protein catabolism.
3. This study in vivo examines the effects of chronic metabolic acidosis on the relationship between growth, nitrogen disposal and skeletal muscle catabolism in the rat.
4. Growth, nitrogen utilization and acquisition of body mass were significantly impaired in acidotic animals compared with pair-fed controls.
5. Total nitrogen excretion was significantly increased in acidotic rats despite decreased urea production. The time course of this response to acidosis was synchronous with that of accelerated protein catabolism in skeletal muscle.
6. It is proposed that metabolic acidosis impairs growth by stimulating skeletal muscle protein catabolism. It is suggested that this forms part of a co-ordinated multi-organ homoeostatic response to acidosis, skeletal muscle and down-regulated urea production supplying the nitrogen required for renal ammoniagenesis.
Effect of destruction of the vascular endothelium upon pressure/flow relations and endothelium-dependent vasodilatation in resistance beds of spontaneously hypertensive rats
Authors: Randall Michael D. , Thomas G. Roger , Hiley C. Robin 
Published: August 2015

1. Pressure/flow relationships were determined in the in situ blood-perfused superior mesenteric and hindquarters vascular beds of spontaneously hypertensive rats and Wistar-Kyoto normotensive rats before and after destruction of the endothelium with detergent. The effects of indomethacin on the regression of pressure on flow were also investigated in the spontaneously hypertensive rats, as were the endothelium-dependent relaxations in response to carbachol in the mesenteric bed.
2. In the spontaneously hypertensive rats the regression line of pressure on flow in the two vascular beds was both steeper and more elevated than in the Wistar-Kyoto rats, showing that there was greater resistance to flow in the hypertensive animals. Destruction of the endothelium significantly increased the slope of the regression in both Wistar-Kyoto and spontaneously hypertensive rats: the increases in the Wistar-Kyoto rats were 2.4 ± 0.3 fold (mesenteric) and 2.0 ± 0.5 fold (hindquarters) which were comparable with the respective increases of 1.6 ± 0.3 fold and 1.8 ± 0.3 fold in the spontaneously hypertensive rats.
3. Indomethacin (5 mg/kg, intravenously) had no effect on the pressure/flow relations in either of the vascular beds of the spontaneously hypertensive rats.
4. The dose-response curves for the endothelium-dependent vasodilatation in response to carbachol were not significantly different in spontaneously hypertensive and Wistar-Kyoto rats.
5. The results suggest that tonic release of endothelium-derived relaxing factor has similar effects in modulating resistance vessel tone in vivo in both hypertensive and normotensive rats. Further, endothelium-dependent vasodilatation does not appear to be impaired in the mesenteric vasculature in spontaneously hypertensive rats, and there appears to be no significant modulation of mesenteric vascular resistance by tonic release of cyclo-oxygenase products in spontaneously hypertensive rats.