bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences in serum lipids and lipoproteins at birth
Authors: CARLSON LARS A. , HARDELL LARS IVAR
Published: March 2008

Abstract. In a study of 1426 males and 1391 females at birth the mean concentrations of cholesterol in total serum, in the sum of very low density and low density lipoproteins and in high density lipoprotein were significantly higher in females than in males. No sex difference was present in the concentration of triglycerides either in total serum or in the lipoprotein fractions.
A reassessment of intravascular volume measurements in protein—calorie malnutrition
Authors: FONDU P.
Published: March 2008

Abstract. Accurate determination of plasma volume is difficult in oedematous protein–calorie malnutrition, but present studies on the equilibration of labelled red cells have shown that red cell volume measurements are valid in this syndrome. The red cell volumes have been measured in afflicted Bantu children during a refeeding programme. Expression of the results in ml/kg, ml/m2 or ml/cm is misleading and has been replaced by expressing the results as a percentage of the means of the normal values for the height. The results show that the red cell volume increase that ought to occur at the end of re‐feeding programme (and hence the iron requirement) is far higher than suggested by the packed cell volume. With treatment the red cell volume increases slowly. The red cell volume and plasma volume changes that occur during treatment do not take place at the same rate.
Composition of the glomerular basement membrane in the congenital nephrotic syndrome of the Finnish type*
Authors: TRYGGVASON KARL
Published: March 2008

Abstract. The composition of the glomerular basement membrane (GBM) was studied in three patients with the congenital nephrotic syndrome of the Finnish type (CNF). A decrease was found in the relative amounts of amino acids characteristic of collagen, i.e. 3‐hydroxyproline, 4‐hydroxyproline, hydroxylysine and glycine. The decrease in hydroxyproline was also apparent in the ratio of 4‐hydroxyproline to proline and in direct assays of 4‐hydroxyproline in whole glomeruli. The ratio of 3‐hydroxyproline to 4‐hydroxyproline was decreased by about 40%. Slight increases were found in the amounts of some amino acids. No significant change was found in the glucose content of the GBM whereas the galactose content was slightly decreased. The results suggest a decrease in the relative amount of the collagen component in the GBM of CNF patients, but a decrease in the relative amount of 3‐hydroxyproline indicates that other changes also exist.
Mechanism of oestrogen and progesterone effects on lipid and carbohydrate metabolism: alteration in the insulin: glucagon molar ratio and hepatic enzyme activity
Authors: MANDOUR T. , KISSEBAH A. H. , WYNN V.
Published: March 2008

Abstract. As in women receiving oestrogens the administration of 17β‐oestradiol to ovariectomized female rats caused a rise in fasting plasma triglycerides and a fall in plasma glucose. Progesterone, on the other hand, had no significant effects.

In the oestradiol treated rats, the portal vein basal insulin levels were slightly reduced. Oestradiol, however, had a marked suppressive effect on the alpha cells of the pancreas resulting in a greater reduction in basal glucagon and impaired glucagon response to alanine infusions. The relative insulin to glucagon (I/G) molar concentration ratio in portal vein blood was increased. Oestradiol also produced a dose dependent increase in the activity of the liver lipogenic enzymes, acetyl CoA carboxylase and fatty acid synthetase. On the other hand, the activity of the gluconeogenic rate limiting enzyme phosphoenol‐pyruvate carboxykinase (PEPCK) was inhibited. The cross‐over pattern of gluconeogenic intermediates confirmed inhibition of gluconeogenesis at this step, an effect which is similar to that induced by relative insulin ‘excess’.

Progesterone produced an increase in the portal vein insulin concentrations. Both the basal and the alanine‐stimulated glucagon levels were also increased. The I/G molar ratio in portal vein blood of progesterone treated rats remained unaltered and the hepatic lipogenic and gluconeogenic enzyme activities were similar to control animals.

These data suggest that insulin activity is increased relative to glucagon in the liver of oestradiol‐treated rats due to the rise in portal vein I/G ratio. The changes in liver lipogenic and gluconeogenic enzymes and the alterations in fasting plasma triglycerides and glucose in response to oestrogens could be secondary to this effect.
Lipoprotein‐X: a substrate for lecithin: cholesterol acyltransferase
Authors: PATSCH JOSEF R. , SOUTAR ANNE K. , MORRISETT JOEL D. , GOTTO ANTONIO M. , SMITH LOUIS C.
Published: March 2008

Abstract. The action of lecithin:cholesterol acyltransferase (LCAT) was studied on an abnormal lipoprotein (LP‐X) rich in phosphatidylcholine and cholesterol from the plasma of patients with obstructive liver disease. 60 mg LP‐X isolated free of other lipoproteins and subsequently labelled with 3H‐cholesterol were incubated with 1 mg highly purified enzyme in the presence of albumin. After 45 h at 37°C, the incubation mixture was subjected to zonal ultracentrifugation. 3H‐cholesteryl esters were quantified in each fraction of the zonal gradient. More than 95% of the lipoproteins in this mixture banded in the density range of LP‐X with no change in size distribution, but did contain 593 nmoles of newly formed cholesteryl esters. Agarose electrophoresis revealed an α‐migrating band in addition to the original β‐band. Also, on agar, the typically cathode migrating LP‐X was changed to anode moving material.

These studies indicate that LP‐X can serve as a substrate for LCAT.
Impairment of drug metabolism in patients with liver cancer
Authors: SOTANIEMI EERO A. , PELKONEN R. OLAVI , MOKKA RISTO E. , HUTTUNEN RISTO , VILJAKAINEN EILA
Published: March 2008

Abstract. Drug metabolizing capacity was investigated in sixteen patients with cancer in the liver by comparing in vivo (antipyrine disappearance rate from plasma) and in vitro (cytochrome P‐450, benzpyrene hydroxylase, and 7‐ethoxycoumarin O‐deethylase activities in liver biopsies) indices of drug metabolism with the condition of tumour‐free liver parenchyma and with biochemical liver function tests. Drug metabolism was impaired as antipyrine hydroxylation was significantly lower than in matched controls. Impairment of antipyrine metabolism was related to the pathological changes in the liver; patients with metastatic liver cancer or with tumour and cirrhosis metabolized antipyrine at a reduced rate, whereas those with a hepatoma occupying from 20 to 80% of the liver volume had normal antipyrine metabolism. Liver enzyme activities were related to the site of the biopsy; values were low in and around the tumour tissue and high in normal parenchyma. The antipyrine half‐life was related to serum albumin concentration but not to other liver function tests. The results demonstrate that in liver cancer patients the drug‐hydroxylating capacity is dependent on the ability of the tumour‐free parenchyma to metabolize drugs. Hence quantitative evaluation of liver changes together with tests measuring liver synthetic capacity might be of significance when predicting drug metabolism in patients with hepatic malignancy.
Studies on the biosynthesis of albumin and proteins in human liver tissue
Authors: LUNDHOLM KENT , SCHERSTÉ TORE , LINDSTEDT GÖRAN , LUNDBERG PER‐ARNE
Published: March 2008

Abstract. The incorporation rate of leucine into albumin and the incorporation rate of leucine into hepatic proteins were determined in human liver tissue slices.

Leucine was linearly incorporated into hepatic tissue albumin, into albumin released into the incubation medium, and into hepatic proteins during 4 h incubation. Amino acids stimulated the albumin and hepatic protein synthesis in vitro and in vivo. The incorporation rate of leucine into hepatic albumin and tissue proteins was correlated to hepatic RNA concentration.

In twenty‐one experiments the mean incorporation rate of leucine into hepatic tissue immunoreactive albumin was 5.1±0.6 μmol leucine h‐1 g albumin‐1 (mean±; SEM), and 0.87±;0.17 μmol leucine h‐1 g albumin‐1 into albumin released to the incubation medium. By crossed immunoelectrophoresis, the hepatic immunoreactive albumin could be partly resolved into two components one of which migrated at the same rate and the other at a lower rate than serum albumin. Treatment of the slowly migrating component with a low concentration of trypsin changed its mobility to that of serum albumin. Gel filtration through Sephadex G‐100 of the slowly migrating fraction showed that it had similar molecular size as that of serum albumin. The results support the hypothesis that human hepatic albumin biosynthesis involves a polypeptide precursor similar to that described for the rat liver.
Total serum haemolytic complement activity, erythrocyte sedimentation rate and plasma fibrinogen as indicators of the stage in Hodgkin's disease
Authors: WAGENER D. J. THEO , HAANEN CLEMENS
Published: March 2008

Abstract. Total serum haemolytic complement activity, plasma fibrinogen, erythrocyte sedimentation rate and other biological values in forty‐three patients with Hodgkin's disease were correlated with results of staging.

A highly significant increase (P = 10‐5) of the mean total serum haemolytic complement activity was found in stages IIIA and IVA and in all stages with systemic symptoms. The complement activity in patients with less extensive disease without systemic symptoms (stages IA and IIA) did not show a significant increase over the controls.

The best initial parameters correlating well with disease activity were complement activity, ESR and fibrinogen level. It is concluded that total serum haemolytic complement activity gives additional information and can be helpful in differentiating between favourable and unfavourable forms of Hodgkin's disease.
Immunoreactive prolyl hydroxylase in human skin, serum and synovial fluid: changes in the content and components with age
Authors: TUDERMAN LEENA , KIVIRIKKO KARI I.
Published: March 2008

Abstract. The concentration of immunoreactive prolyl hydroxylase was measured in human skin, serum and synovial fluid. In skin concentrations of the immunoreactive enzyme protein and the enzyme activity were highest in foetuses, at an intermediate level in 0–1‐year‐old children and lowest in adults. About 13–19% of the enzyme protein in foetal skin was in the active form compared with 2–4% in the adult. Concentrations of immunoreactive prolyl hydroxylase in serum were lower than in skin and no changes were found with age. The concentration of immunoreactive prolyl hydroxylase in synovial fluid of the knee joint in patients with traumatic effusion was about half that found in serum.

The ratio of enzyme tetramer, which is the active form of the enzyme, to the total immunoreactive protein was studied by gel filtration. In foetal skin, about 15–20% of the total immunoreactive protein was present in tetramer form, and a good correlation was found between the ratio of enzyme tetramer to the total immunoreactive protein and the ratio of enzymic activity to the concentration of total immunoreactive enzyme. Small amounts of enzyme tetramer were found in the serum and synovial fluid. The data suggest that the activity of prolyl hydroxylase in human tissues may be partly controlled by a mechanism involving changes in the ratio of the active enzyme tetramer to total enzyme protein.
The regulation of sterol biosynthesis in leucocytes of subjects with familial hypercholesterolaemia
Authors: HIGGINS M. J. P. , GALTON D. J.
Published: March 2008

Abstract. The regulation of sterol synthesis and 3‐hydroxy‐3‐methylglutaryl CoA reductase (HMG‐CoA reductase) activity in leucocytes has been studied in seventy‐five subjects of whom thirteen had familial hypercholesterolaemia (heterozygous). The activity of HMG‐CoA reductase in leucocytes was closely parallel to the incorporation of 14C‐acetate into sterols over a wide range of activities, suggesting that the enzyme is ratedetermining for the pathway. When six obese subjects were placed on an acaloric diet for 7 days sterol synthesis declined by 75% in adipocytes but was unaffected in leucocytes. A low cholesterol diet (< 250 mg/day) for 7 days did not affect sterol synthesis in either cell type.

In subjects with familial hypercholesterolaemia (heterozygous) the enzyme tended to increase to higher levels than controls when leucocytes were incubated in a lipid‐deficient medium; but a more marked abnormality was a failure of suppression of the enzyme when leucocytes from affected subjects were returned for 8 h to a medium containing low‐density lipoprotein. In one kindred the index patient with severe heterozygous familial hypercholesterolaemia had a normally regulated enzyme whereas his affected siblings (brother and sister) showed incomplete suppression of the enzyme by low‐density lipoprotein.

It is concluded that loss of regulation of HMG‐CoA reductase may be phenotypically linked to the origin of familial hypercholesterolaemia and in most cases provides a useful genetic marker for the disease.
The effect of pindolol on plasma renin activity in patients with essential hypertension
Authors: TÉNYI I. , NÉMETH M. , JÁVOR T. , NEMES J. , CZIMER J.
Published: March 2008

Abstract. Twenty‐two patients with essential hypertension were treated for 3 months with pindolol, and blood pressure and plasma renin activity were measured at rest and after stimulation (upright posture stimulation and insulin induced hypoglycaemia stimulation).

Beta‐receptor blockade produced a significant decrease in systolic and diastolic blood pressure.

After treatment with pindolol the plasma renin activity was significantly lower. Under conditions of renin stimulation such as orthostasis and insulin produced hypoglycaemia, plasma renin activity was significantly lower in treated patients.

There was no correlation between the fall of plasma renin activity and the decrease of blood pressure. Renin suppression is probably only one of the factors involved in the reduction in the blood pressure in these patients.
The effect of beta‐adrenergic blockade on patterns of urinary sodium excretion, blood pressure and plasma renin activity in patients with essential and renovascular hypertension
Authors: SALVETTI A. , SASSANO P. , POLI L. , PEDRINELLI R. , ARZILLI F.
Published: March 2008

Abstract. The effects of β‐adrenergic blockade, using oxprenolol, were studied on plasma renin activity, urinary sodium excretion and blood pressure in ten normal subjects and in 120 patients with essential and renovascular hypertension.

Blood pressure was reduced by oxprenolol administration. The hypotensive action of the drug was independent of either the basal plasma renin activity or of the plasma renin activity response.

Oxprenolol decreased plasma renin activity in normal subjects and in patients with essential hypertension with normal or high basal plasma renin activity. Patients with low plasma renin activity may show a lack of response to the beta‐blockade.

In patients with renovascular disease the response of plasma renin activity to oxprenolol was not a discriminant factor between patients cured or not cured by surgery. Some renovascular patients were unresponsive to beta‐blockade with oxprenolol.
Serum octopamine, coma, and charcoal haemoperfusion in fulminant hepatic failure
Authors: CHASE R. A. , TREWBY P. N. , DAVIS M. , WILLIAMS ROGER
Published: March 2008

Abstract. Serum octopamine levels were significantly higher in twenty patients with fulminant hepatic failure (FHF) during the first 48 h of grade IV coma than in healthy control subjects (3.38 ± 0.20 ng/ml and 1.75 ± 0.19 ng/ml respectively, P<0.001). Serial measurements in five patients who died without regaining consciousness showed serum octopamine to remain raised, and concentrations in the cerebrospinal fluid at death reflected serum levels. In five patients who regained consciousness, improvement in encephalopathy was associated with a significant reduction in serum octopamine. Renal failure in patients with FHF was found to contribute to raised serum octopamine but could not alone account for the observed levels. Patients given neomycin therapy did not have significantly lower serum octopamine levels than an untreated group. There was, however, a significant correlation between elevated serum octopamine and the occurrence of gastrointestinal bleeding during the previous 24 h. Charcoal haemoperfusion did not appreciably reduce serum octopamine levels.
Adrenaline‐sensitive adenylate cyclase of human fat cell ghosts: properties and hormone‐sensitivity
Authors: KATHER HORST , GEIGER MAGDALENE
Published: March 2008

Abstract. Some of the properties of the human fat cell adenylate cyclase were studied in fat cell ghosts prepared from subcutaneous adipose tissue of twenty‐three patients. Under standard assay conditions (1 mmol/l ATP, 5 mmol/l mg2+, pH 8.5), the basal activity ranged from 0.6 nmol to 4.4 nmol of 3′,5′‐cyclic AMP formed per mg protein per 15 min.

Peptide hormones (ACTH, glucagon) were ineffective in stimulating adenylate cyclase. Adrenaline, however, induced a 1.5–5‐fold enhancement of 3′‐5′‐cyclic AMP formation.

The rates of basal and hormone‐stimulated enzymic activity were maximal at pH 8.5. The relative extent of hormonal stimulation, however, was greater at pH 7.4.

ATP in excess of magnesium had an inhibitory effect on basal and hormone‐stimulated enzymic activity. Magnesium in excess of ATP caused a concentration‐dependent increase of both expressions of enzymic activity.

Of the guanine nucleotides, GTP (0.1 mmol/l) augmented hormone sensitivity via a preferential inhibition of basal activity. 5′‐Guanylyl‐imidodiphosphate, however, caused a 2–5‐fold increase of basal and adrenaline‐stimulated activities.

The results show that human fat cell ghosts contain an adrenaline‐sensitive adenylate cyclase system, whose hormone sensitivity is profoundly influenced by ATP, magnesium ions, pH, and guanine nucleotides. Artificial cofactors such as 5′‐guanylyl‐imidodiphosphate or α‐blocking agents are not essential for the expression of hormone sensitivity.
Renin levels and spironolactone treatment in general practice: similar blood pressure lowering effect of spironolactone in low and normal renin patients
Authors: SUNDSFJORD J. A. , ØDEGAARD A. E.
Published: March 2008

Abstract. We examined the predictive value of plasma renin activity (PRA) in ambulatory patients in the selection of hypertensive patients for treatment with spironolactone. The patients were classified as frusemide responders or non‐responders according to their PRA response to 80 mg frusemide orally.

After an initial 4 weeks placebo period forty‐five patients with the clinical diagnosis of benign hypertension (WHO stage I‐II) entered a 4 × 4 week double blind treatment period during which they received spironolactone (Aldactone®) 400, 300, 200 and 100 mg/day, respectively.

Five out of the forty‐five patients who started the trial were withdrawn on account of side‐effects and five patients for other reasons. Of the thirty‐five patients who completed the study eighteen belonged to the group of non‐responders to frusemide, seventeen to the responders.

A gradual and significant decrease in mean blood pressure occurred during the period with the high doses of spironolactone, without any significant difference between the groups. The blood pressure lowering effect obtained with the initial high doses was maintained during the consecutive periods when the doses was reduced to a half or even a fourth, in both groups.

We conclude that PRA measurement in ambulatory patients is of little, if any, value for the selection of hypertensives for spironolactone treatment; this in contrast to similar selections performed on hospitalized patients.
Thyroid hormone concentrations and inhibition of thyroid stimulating hormone secretion in euthyroid subjects with autonomous thyroid nodules
Authors: CARPI A. , BIANCHI R. , ZUCCHELLI G. C. , TONI M. G. , COLI A. , LEVANTI C. , MARIANI G.
Published: March 2008

Abstract. Sixty‐four euthyroid patients with autonomous thyroid nodules and normal thyroxine (T4) concentrations and tri‐iodothyronine resin uptake have been studied. The serum tri‐iodothyronine (T3) concentration of the patients was 2.24 (±0.67) ng/ml, significantly higher than in a group of fifty‐seven euthyroid control subjects (1.58 ± 0.30 ng/ml). When no extranodular tissue was visible on the basal thyroid scan, the T3 was 2.31 (±0.63) ng/ml, significantly higher than in patients with some extranodular uptake on the basal scan (1.91 ± 0.42 ng/ml). There was no significant difference in the serum T4 concentrations of the patients (7.37 ± 2.10 μg/100 ml) compared to the control group (6.88 ± 1.89 μg/100 ml). The T4 concentrations were not correlated with total or partial inhibition of the extranodular tissue. The thyroid hormone concentrations were not directly correlated to the size of the nodule assessed by scan imaging. The thyroid stimulating hormone (TSH) concentration of the patients (1.52 ± 0.38 μU/ml) was significantly lower than in normals (2.49 ± 0.96 μU/ml). No significant difference was found in the TSH concentrations of patients with partial or total inhibition of extranodular tissue irrespective of the T3 concentration. A thyrotrophin releasing hormone stimulation test in twelve patients did not increase the serum TSH, irrespectively of the T3 concentration.

These data show the high frequency of elevated serum T3 concentrations despite normal serum T4 concentration in euthyroid patients with autonomous thyroid nodules. They confirm that inhibition of TSH secretion can occur when thyroid hormone concentrations are in the normal range.
Acid‐base induced alterations in glutamine metabolism and ureogenesis in perfused muscle and liver of the rat
Authors: OLIVER J. , KOELZ A. M. , COSTELLO J. , BOURKE E.
Published: March 2008

Abstract. The effects of altered acid‐base balance on the production of urea and the metabolism of glutamine were investigated in the isolated perfused liver and hind‐quarter of the rat. In the isolated perfused rat liver, lowering of perfusate pH without altering bicarbonate concentration significantly reduced urea production and increased net glutamine synthesis, although the converse did not obtain. In the isolated perfused rat hindquarter when perfusate pH and bicarbonate were simultaneously reduced glutamine synthesis was significantly increased. The combined hepatic and muscle increase in glutamine synthesis accounted for 89% of the decrease in hepatic urea synthesis under these experimental conditions. These changes in nitrogen metabolism are interpreted in terms of adaptations which offset the initial alterations in hydrogen ion homeostasis.
The brush border membrane in hereditary sucrase—isomaltase deficiency: abnormal protein pattern and presence of immunoreactive enzyme
Authors: FREIBURGHAUS A. U. , DUBS R. , HADORN B. , GAZE H. , HAURI H. P. , GITZELMANN R.
Published: March 2008

Abstract. In a child with hereditary sucrase‐isomaltase deficiency immunoreactive enzyme was present in the intact duodenal mucosa. Polyacrylamide gel electrophoresis carried out with membrane fragments of an intestinal biopsy showed an abnormal protein band without enzyme activity. The mucosa had a relatively high residual isomaltase activity which was recovered from the gel in a position suggesting higher than normal molecular weight. The results indicated that in this patient the primary structural defect was in the sucrase moiety which was enzymatically inactive. The isomaltase subunits may have aggregated into a large molecular weight complex because of unavailability of their partners. The observation also provided evidence for separate biosynthesis of the two moieties of the sucrase‐isomaltase complex.
Effects of the angiotensin II antagonist 1‐sar‐8‐ala‐angiotensin II in hypertension in man
Authors: FAGARD R. , AMERY A. , LIJNEN P. , REYBROUCK T.
Published: March 2008

Abstract. The angiotensin II antagonist 1‐sar‐8‐ala‐angiotensin II (saralasin) was infused in forty‐six patients with hypertension of various aetiology (essential, renal arterial or parenchymal disease, primary hyperaldosteronism), before and/or during sodium volume depletion obtained by chlorthalidone and low sodium diet. When saralasin was infused in twenty‐five patients ingesting 130 mmol of sodium per day, including patients with proven renovascular hypertension, the changes in mean arterial pressure ranged from +10 to ‐7 mmHg (mean: +0.20 mmHg) and were not related to the plasma renin concentration (PRC) (r= ‐0.11). During sodium volume depletion, saralasin induced changes in mean arterial pressure, ranging from +21 to ‐76 mmHg, which were closely related to log PRC (n= 32; r= ‐0.87). Combined sodium depletion and antagonism of angiotensin II ‘normalized’ mean arterial pressure (≤100 mmHg) in twenty‐one of the thirty‐two patients, while pressure remained between 106 and 147 mmHg in eleven ‘poor’ responders, so that pressor mechanisms other than sodium volume and angiotensin must be responsible for the remaining elevation of pressure in these patients.

The study indicates that arterial pressure is not dependent on the immediate pressor effects of angiotensin II in sodium replete patients, and in sodium deplete subjects whose PRC remains low, while it is at least partly angiotensin II dependent during sodium volume depletion in the others. The results cast doubts on the clinical usefulness of saralasin in the investigation of patients with hypertension, when studied in the conditions of the present study.
The role of adrenaline and of the vagus in gastrin release and acid secretion in dogs
Authors: BRANDSBORG O. , ØRNSHOLT J. , BRANDSBORG M. , CHRISTENSEN N. J.
Published: March 2008

Abstract. Serum gastrin, gastric acid secretion and plasma adrenaline in response to intravenous injection of 2‐deoxy‐D‐glucose and to insulin were measured in six dogs with gastric fistulae before and after denervation of the antrum and the intestine (antral‐intestinal vagotomy). Serum gastrin and gastric acid secretion were also measured in the same dogs during intravenous infusion of adrenaline in doses which produced an elevation of plasma adrenaline to levels occurring during hypoglycaemia and after the injection of 2‐deoxy‐D‐glucose.

Antral‐intestinal vagotomy reduced basal gastrin concentration slightly and basal gastric acid secretion considerably. The rise in serum gastrin in response to 2‐deoxy‐D‐glucose and hypoglycaemia was abolished while the increase in gastric acid secretion was reduced after antral‐intestinal vagotomy. Beef meal‐stimulated gastrin secretion was the same before and after vagotomy. Intravenous infusion of adrenaline had no effect on either serum gastrin or gastric acid secretion.

It is concluded that in the dog, in contradistinction to man, gastrin release after insulin is dependent on an intact vagus. Release of gastrin by adrenaline in the dog does not appear to be physiological since it is not achieved by the amount of adrenaline released in response to hypoglycaemia.
Effects of racemic, dextro‐laevo‐propranolol and isoxuprine on the metabolic and endocrine response to cold in the newborn rabbit
Authors: CSER A. , GIRARD J. , GOODE M. , LEACH F. N. , ASSAN R. , MILNER R. D. G.
Published: March 2008

Abstract. The effect of racemic, dextro‐, laevo‐propranol or isoxuprine on the plasma glucose, free fatty acid (FFA), insulin, glucagon and glucocorticoid concentration was studied in rabbits aged 3–5 days at 35°C and after exposure to 25°C for 3 h. Cold exposure alone caused a large rise in plasma FFA and a significant rise in plasma insulin and glucocorticoids. At 35°C laevo‐propranolol depressed both plasma FFA and glucose where‐as dextro‐propranolol caused a significant rise in plasma glucose, FFA, insulin and glucagon and a fall in plasma glucocorticoid concentration. Racemic propranolol resembled the laevo‐isomer in depressing plasma FFA and the dextro‐isomer in stimulating plasma insulin and glucagon but had no effect on the mean plasma glucose concentration. Isoxuprine caused a rise in plasma FFA and insulin levels. At 25°C laevo‐propranolol blocked the cold‐induced rise in plasma FFA, caused a rise in plasma insulin and an insignificant drop in plasma glucose. The effects of dextro‐propranolol seen at 35°C were abolished by exposure to 25°C. Racemic propranolol resembled the laevo‐isomer in partially blocking the rise in plasma FFA. Isoxuprine exaggerated the rise in plasma FFA and caused a significant fall in plasma glucagon concentration. Incubation of pieces of pancreas in vitro from rabbits aged 3–5 days or 5–7 weeks with the three types of propranolol at concentrations of 0.2, 2.0 and 20.0 μg/ml had no effect on basal or glucose stimulated insulin secretion. Racemic propranolol at concentrations of 40 and 60 μg/ml and laevo‐propranolol at 80 μg/ml inhibited insulin release stimulated by glucose from pancreas of 5–7 week rabbits in vitro.
Urinary kallikrein and changes in endogenous aldosterone in the rat
Authors: MIMRAN ALBERT , BAUDIN GÉRARD , CASELLAS DANIEL , SOULAS DOMINIQUE
Published: March 2008

Abstract. Urinary kallikrein excretion was studied during changes in sodium intake. The effect of short‐term (5 days) and long‐term (4 weeks) sodium restriction was also investigated. In order to provide additional evidence for a primary role of endogenous aldosterone on the renal kallikrein system, the effect of dietary potassium restriction was studied in chronically sodium depleted rats.

Chronic (4 weeks) sodium restriction was associated with high urinary kallikrein excretion (6.21 ± 0.31 i.u./24 h/100 g body weight). Urinary kallikrein was lower in high salt and normal salt rats (2.38 ± 0.18 and 2.71 ± 0.18 i.u./24 h/100 g bw). A negative correlation (r= ‐0.88, P<0.001) between urinary kallikrein and the logarithm of natriuresis was obtained.

Positive correlations between urinary kallikrein and diuresis were obtained within each group of rats equilibrated with different sodium intakes.

When chronically sodium loaded rats were given a low sodium diet for a 5‐day period, urinary kallikrein increased from 1.99 ± 0.17 to 3.64 ± 0.3 i.u./24 h/100 g bw (P<0.001). The mean value achieved after 5 days of sodium restriction was significantly lower (P<0.001) than the value obtained in long‐term (4 weeks) sodium depleted rats.

When low sodium rats were fed a low sodium‐low potassium diet for 7 days, urinary kallikrein decreased by 34 ± 8% (P<0.005) and urinary aldosterone fell from 112 ± 27 to 43 ± 11 ng/24 h (P<0.01). Natriuresis remained constant throughout the study.

These results suggest that endogenous aldosterone is one of the main determinant of renal kallikrein activity. Kallikrein may participate in the regulation of water excretion. In addition, the kallikrein‐kinin system may be involved in the renal adaptation to long‐term sodium restriction in the rat.
A radioimmunoassay for human thyroglobulin: methodology and clinical applications
Authors: PEZZINO V. , COZZANI P. , FILETTI S. , GALBIATI A. , LISI E. , SQUATRITO S. , VIGNERI R.
Published: March 2008

Abstract. A specific double‐antibody radioimmunoassay with a sensitivity of 2.5 ng/ml has been developed for measuring thyroglobulin (Tg) in human serum. As endogenous anti‐Tg antibodies in serum interfere in the assay, only sera with a negative tanned red cell (TRC) test are suitable for analysis. Tg was detectable in 84.7% of the euthyroid subjects, with a mean value of 6.1 (values ranging from nondetectable to 43.0 ng/ml). Values were significantly higher in women than in men. Tg release by the thyroid appears to be under pituitary control, as suggested by TSH stimulation and T3 suppression tests. Elevated Tg levels were found in hyperthyroidism, simple goitre, and differentiated thyroid carcinoma. The significance of circulating Tg and the possible application of the Tg RIA are discussed.
Cholestyramine and ileal by‐pass in the treatment of familial hypercholesterolaemia
Authors: MIETTINEN T. A. , LEMPINEN M.
Published: March 2008

Abstract. A comparison was made of the therapeutic effectiveness of cholestyramine and an ileal by‐pass operation as hypocholesterolaemic measures in thirteen patients with familial xanthomatotic type II hypercholesterolaemia. Serum cholesterol and faecal steroids were measured before and at the end of a 10 day course of cholestyramine (32 g/day), and subsequently after an ileal by‐pass operation. The mean decrease in serum cholesterol caused by cholestyramine (‐17%) was significantly less than that caused by the surgical procedure (‐33%). The increase in faecal steroid excretion, mainly as bile acids, was lower with cholestyramine (1.261 g/day) than after the ileal exclusion (2.176 g/day) and a positive correlation was found between the decrease in serum cholesterol and the increase in the faecal elimination of steroids of cholesterol origin. However, even though the increase in faecal steroids with cholestyramine was positively correlated with that resulting from ileal by‐pass, the correlation between the corresponding changes in serum cholesterol level was not significant. The findings indicate that ileal by‐pass decreases serum cholesterol and increases faecal elimination of cholesterol more effectively than cholestyramine, and that the decrease in the serum cholesterol level induced by ileal exclusion is not consistently predictable by the serum cholesterol response to the preceding cholestyramine treatment.
Effects of prostaglandin‐E1 on ST segment elevation and regional myocardial blood flow during experimental myocardial ischaemia in dogs
Authors: RIEMERSMA RUDOLPH A. , TALBOT RICHARD C. , UNGAR ALEX , MJØS OLE D. , OLIVER MICHAEL F.
Published: March 2008

Abstract. The effects of prostaglandin E1 (PGE1) on myocardial ischaemia (as measured by epicardial ST segment changes), myocardial flow and substrate exchange has been studied in dogs. Myocardial ischaemia was induced by intermittent external clipping of a branch of the left anterior descending coronary artery.

During occlusion with a continuous intravenous infusion of isoprenaline, elevated epicardial ST segments (∑ST), were raised to 46 ± 6 mV (mean ± SEM). Pretreatment with PGE1 reduced ∑ST to 34 ± 6 mV (P<0.001), but had no effect on mean aortic blood pressure (AP¯) or on regional myocardial blood flow. Isoprenaline infusion increased plasma free fatty acids (FFA) to 1925 ± 150 μmol/l and this was reduced to 1320 ± 220 μmol/l by PGE1 (P<0.005).

During occlusion without isoprenaline, PGE1 did not effect ∑ST or plasma FFA when infused intravenously or into the left atrium. Mean aortic blood pressure decreased from 131 ± 7 to 108 ± 10 (PGE1 i.v.) or 109 ± 8 mmHg (PGE1 i.a.) (P<0.001). This was associated with a decrease in regional myocardial blood flow, both in the ischaemic and non‐ischaemic myocardium. However, when blood pressure was maintained constant, intravenous PGE1 tended to decrease occlusion‐induced ST segment elevation.

These results suggest that PGE1 can reduce isoprenaline‐stimulated myocardial ischaemia through its antilipolytic action but in the absence of catecholamine stimulation the main effect is to reduce blood pressure thereby counterbalancing any potentially beneficial effects on the ischaemic myocardium.
Studies on the degradation of lipoprotein‐X
Authors: PATSCH W. , PATSCH J. R. , KUNZ F. , SAILER S. , BRAUNSTEINER H.
Published: March 2008

Abstract. Three patients suffering from prolonged obstructive jaundice were studied after surgical removal of biliary obstruction. Four days after surgery the initial cholesterol esterification rate in the plasma rose from very low activities to values three to four times higher than those found in normal subjects. During this time lipoprotein‐X decreased in concentration. The initial cholesterol esterification rate returned to normal values when plasma lipids and lipoproteins reached normal levels.

During incubation of normal plasma with lipoprotein‐X, changes in the lipid composition of the incubation mixture were observed which appeared to be catalysed by lecithin:cholesterol acyltransferase. The formation of esterified cholesterol and lysophosphatidylcholine exceeded that of control experiments when lipoprotein‐X was replaced by buffer solution in the incubation mixture. Lipoprotein‐X disappeared as monitored by electrophoresis on agar and measured after zonal ultracentrifugation, and lipoproteins with flotation behaviour of high density lipoprotein2, enriched in polar lipids, appeared.

When plasma was incubated separately with lipoprotein‐X1 and lipoprotein‐X2in vitro, the T1/2 of these lipoproteins were 24 h and 9 1/2 h, respectively. Addition of lipoprotein‐X2 to normal plasma resulted in an increased initial cholesterol esterification rate with a sigmoidal response curve. Lipoprotein‐X1 increased the initial cholesterol esterification rate also but to a lesser extent.

Our findings indicate that incubation of normal plasma with lipoprotein‐X results in the disappearance of this abnormal lipoprotein and the appearance of a high density lipoprotein2‐like particle mediated by enzymic cholesterol acyltransfer.
Arterial and coronary sinus catecholamines and cyclic‐AMP during dynamic supine exercise in patients with chest pain
Authors: ROBSON R. H. , CARRUTHERS M. , FLUCK D. C.
Published: March 2008

Abstract. Arterial and coronary sinus catecholamine concentrations were measured during dynamic exercise in patients to assess the sympathetic response. Arterial concentrations increased from 1.77 nmol/l(SEM = 0.53, n= 7) (control) to 2.95 nmol/l (SEM = 0.65, n= 7) during exercise (0.05 >P>0.01) and coronary sinus concentrations from 2.78 nmol/l (SEM = 0.53, n= 7) (control) to 4.43 nmol/l (SEM = 0.71, n= 7) (0.05 >P>0.01). Resting, and exercise, arterial‐coronary sinus differences in catecholamine concentrations were not statistically significant. In some patients, higher catecholamine concentrations occurred post‐exercise than during exercise. The coronary sinus‐arterial difference in catecholamine concentration during exercise was greatest in the one patient who developed angina pectoris. Cyclic‐AMP concentrations were also measured, but these did not change significantly, consistent with the predominantly noradrenaline response to exercise.
Free fatty acid and carbohydrate metabolism of the working forearm muscle in type IV hyperlipoproteinaemia
Authors: OLSSON ANDERS G. , EKLUND BRITA , RICCARDI GABRIELE , WALLDIUS GÖRAN , KAIJSER LENNART
Published: March 2008

Abstract. Substrate utilization of the working forearm was studied in nineteen patients with hypertriglyceridaemia (HLP) and compared to nineteen normolipidaemic (NLP) subjects, matched with regard to body weight, body height, intravenous glucose tolerance and age. Arterial‐deep venous differences of oxygen, carbon dioxide, free fatty acids (FFA), glucose, lactate and pyruvate was measured. The fractional extraction and oxidation of fatty acids was assessed by intravenous infusion of albumin‐bound [3H]palmitate and [14C]oleate. Measurements were made both in the postabsorptive state and after plasma FFA lowering by nicotinic acid.

The HLP subjects had, before nicotinic acid, higher arterial concentrations, higher turnover rates of palmitate and oleate and higher plasma glycerol concentrations indicating a greater mobilization of FFA. However, the forearm extraction and oxidation of FFA as well as the calculated total body fatty acid oxidation was similar in HLP and NLP subjects. Nicotinic acid decreased arterial concentrations and turnover rates of FFA to the same extent in HLP and NLP groups, the effect being the same for palmitic and oleic acid. Fractional extraction both of palmitic and of oleic acid increased after nicotinic acid in the NLP but not in the HLP group. Plasma glycerol decrease after nicotinic acid was of the same magnitude in HLP and NLP groups.

Thus, (1) an increased uptake of FFA in HLP subjects must occur in other tissues than skeletal muscle and with another fate of the fatty acids than oxidation. The explanation might be an increased incorporation of fatty acids into triglycerides which are subsequently secreted from the liver. (2) The impaired triglyceride removal in skeletal muscle which has been found in HLP subjects is more likely due to an impaired lipolytic activity than to an abnormality in uptake and utilization of hydrolysed fatty acids.

No abnormalities in carbohydrate metabolism were found in these HLP subjects with normal glucose tolerance.
Blood polymorphonuclear dysfunction in patients with alcoholic cirrhosis
Authors: FELIU EVARIST , GOUGEROT MARIE‐ANNE , HAKIM JACQUES , CRAMER ELISABETH , AUCLAIR CHRISTIAN , RUEFF BERNARD , BOIVIN PIERRE
Published: March 2008

Abstract. Polymorphonuclear leucocyte function was investigated in twenty patients with alcoholic cirrhosis and three patients with cryptogenic cirrhosis. Bacterial ingestion, oxygen‐dependent bactericidal capacity, and chemotactic response were measured. Serum dependent abnormalities were common; they included deficiencies of ingestion and of all subsequent oxygen‐dependent metabolic events (three patients), all oxygen‐dependent metabolic events (one patient), cytochrome c reduction and iodination deficiencies (six patients), isolated cytochrome c reduction deficiency (ten patients), and chemotactic deficiencies (fourteen out of eighteen patients). Serum‐independent abnormalities were much less common; they included increased ingestion rate (four patients), decreased stimulated reduction of nitroblue tetrazolium (three patients), and decreased myeloperoxidase content (eight patients). Polymorphonuclear leucocyte abnormalities are frequent in cirrhosis and may account in part for increased susceptibility to infection in that disease.
Metabolic and hormonal changes after surgery: hyperinsulinaemia during glucose infusion
Authors: SOERJODIBROTO W. S. , HEARD C. R. C. , JAMES W. P. T. , FEW J. D. , BLOOM S. R.
Published: March 2008

Abstract. Serial measurement of blood and urinary hormones and metabolites were made on eleven patients before and after abdominal surgery. A complete nitrogen balance on three patients showed that after the operation there was a net loss of nitrogen equivalent to about 50 g protein per day for 5–6 days.

This period coincided with elevated fasting plasma levels of glucagon and non‐esterified fatty acids (NEFA), and elevated 24 h urinary excretion of free cortisol and 17OH‐corticosteroids; total plasma amino acid levels were diminished but the concentrations of the branchedchain amino acids were increased. Fasting plasma concentrations of glucose, insulin and cortisol were increased only on day 1 after the operation. A 2 h glucose infusion (0.35 g kg‐1 h‐1) was carried out on each patient on day 1 and on ‘recovery’ (9–21 days). The mean glucose levels reached (12.1 mmol and 10.3 mmol/l, respectively) did not differ significantly; they were much higher than in young normal subjects (6.1 mmol/l). Glucose infusions, both on day 1 and on ‘recovery’ resulted in significant depression of glucagon and NEFA levels. Plasma insulin levels during glucose infusion were significantly higher on day 1 than on ‘recovery’, suggesting improving sensitivity to insulin. Possible explanations are discussed. Attention is drawn to the practical implications of the choice of nutrients in the parenteral nutrition of postoperative patients.
Cholesterol and DNA content in arterial tissue in severe obesity: their relation to some risk factors for ischaemic heart disease
Authors: BONDJERS G. , GUSTAFSON A. , KRAL J. G. , SCHERSTÉN T. , SJÖSTRÖM L.
Published: March 2008

Abstract. Arterial tissue was obtained from twelve severely obese patients during jejuno‐ileal by‐pass surgery. The arterial DNA content was inversely correlated with the sum of venous glucose values during an oral glucose tolerance test (rs= ‐0.72). This observation may have implications on the known relationship between decreased glucose tolerance and early manifestations of atherosclerosis.
Human fat cell adenylate cyclase: regional differences in adrenaline responsiveness
Authors: KATHER H. , ZÖLLIG K. , SIMON B. , SCHLIERF G.
Published: March 2008

Abstract. The effect of adrenaline on adenylate cyclase activity in membranes prepared from human abdominal and gluteal adipose tissue was examined. Basal enzyme activity averaged 1.0 nmol cAMP/mg protein/15 min in abdominal tissue and 0.68 nmol cAMP/mg protein/15 min in ghosts from the buttock. Maximally effective concentrations of sodium fluoride (20 mmol/l) induced an eight‐fold increase in both membrane preparations. The maximal response to adrenaline (1.0 mmol/l) averaged 170% in ghosts of abdominal tissue compared with 60% in gluteal membranes. The concentrations of adrenaline required to produce half‐maximal stimulation were similar in membrane preparations of both regions (about 5 × 10‐5 mol/l).
Hepatic collagen proline hydroxylase activity in primary biliary cirrhosis
Authors: JAIN STEPHAN , SCHEUER P. J. , McGEE J. O'D. , SHERLOCK SHEILA
Published: March 2008

Abstract. The enzyme collagen proline hydroxylase has been measured in liver biopsies from fourteen patients with primary biliary cirrhosis. The activity was elevated in ten of the patients, but not to the degree previously found in patients with active cirrhosis. There was no correlation between the enzyme activity and the liver copper concentration, which was elevated in all except one of those measured. This suggests that excessive collagen synthesis in PBC is not directly related to the high liver copper concentrations.
Inhibition of hepatic demethylation of aminopyrine by oral contraceptive steroids in humans
Authors: HEFU REINHARD , KOELZ HANS R. , HAEMMERLI URS P. , BENES IVAN , BLUM ANDRÉ L.
Published: March 2008

Abstract. The effect of oral contraceptive steroids (OCS) on the rate of hepatic demethylation of 14C‐dimethyl‐aminoantipyrine (DAP) was studied directly in healthy young volunteers using a newly developed noninvasive breath analysis technique. After oral administration of a trace dose of DAP the specific activity of 14CO2 in breath was determined during 6 h and expressed as half life. The half life of eighteen female and twelve male control subjects was 2.4 ± 1.2h (2 SD) and 2.2 ± 0.6h (2 SD), respectively. In seven women starting OCS a progressive prolongation of DAP half life during a single menstrual period was observed. In seventeen women who had taken OCS in 21 clay cycles, for more than 3 months, the half life was significantly (P< 0.001) prolonged (4.4 ± 2.1 h) when measured after 21 consecutive days of OCS intake. On average, stopping OCS for 7 days or giving phenobarbital in addition to OCS shortened DAP half life significantly (from 4.4 ± 2.1 h to 3.2 ± 1.1h, n= 17, P 0.005; and from 4.6 ± 2.0 h to 3.2 v 1.0h, n= 12, P<0.01, respectively). Eight of twelve women on OCS responded to OCS intake and to OCS cessation and phenobarbital, whereas four women did not respond to any of these measures. These data suggest that inhibition of hepatic demethylation of DAP by OCS is time dependent and reversible. The extent of inhibition appears to be an individual characteristic of a given person.