bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic HMGCoA reductase in human cholelithiasis: effects of chenodeoxycholic and ursodeoxycholic acids*
Authors: MATON PAUL N. , ELLIS H. JULIA , HIGGINS MALCOLM J. P. , DOWLING R. HERMON 
Published: March 2008

Abstract. To study further the role of hepatic cholesterol synthesis in patients with gallstones, the activity of the rate‐limiting step in cholesterbgenesis, hydroxy‐methyl glutaryl co‐enzyme A reductase (HMGCoAR), was measured in operative wedge liver biopsies from ten patients with untreated cholesterol gallstones, six with pigment stones and ten controls. Hepatic HMGCoAR was also measured in six patients with cholesterol‐rich gallstones treated for 1–24 months with 14‐6‐18‐6 mg chenodeoxycholic acid (CDCA) kg‐1 day‐1, in two patients with radiolucent pigment stones treated with 17‐3 and 17‐7 mg CDCA kg‐1 day‐1 and in ten other patients with cholesterol‐rich stones given 4–5‐7‐2 mg ursodeoxycholic acid kg‐1 day‐1 for 1–6 months. HMGCoAR activity was also related to the free and esterified cholesterol content of both hepatic homogenates and the microsomal fractions.Compared with the controls (HMGCoAR activity 14‐6±1 6 (SEM) pmole mg microsomal protein‐1 min‐1), the mean activity in untreated cholesterol cholelithiasis was 32 2 ±2‐0 (P < 0–001), but was near normal in patients with pigment stones (16‐2 + 1 5). In cholesterol gallstone patients, chenodeoxycholic acid treatment reduced the mean enzyme activity by 51% compared with the untreated gallstone group (P < 0001) and in smaller doses, ursodeoxycholic acid therapy lowered it by 40% (P < 0001) but in the two patients with pigment stones, CDCA did not seem to affect HMGCoAR activity. Despite this four‐fold variation in enzyme activity, there were no significant differences in mean free or esterified cholesterol concentrations in whole liver homogenates or in the microsomal fraction from any of the patient groups.Presented in part at the European Society for Clinical Investigation, Rotterdam, April 1978 (Maton P.N. & Dowling R.H (1978) Eur J Clin Invest 8, 329 (abstract)) and at the V International Bile Acid Meeting, Freiburg, June 1978 (Maton P.N. & Dowling R.H. (1978) in: Biological Effects of Bile Acids (ed. by G. Paumgartner, A. Stiehl and W. Gerok), pp. 91–98. MTP Press, Lancaster).
Purine and pyrimidine metabolism in hereditary orotic aciduria: some unexpected effects of allopurinol
Authors: SIMMONDS H. A. , WEBSTER D. R. , BECROFT D. M. O. , POTTER C. F. 
Published: March 2008

Abstract. Purine and pyrimidine metabolism have been investigated in the longest surviving case of hereditary orotic aciduria after 15 years of chronic uridine therapy. Several unusual features were recorded:1. Although the uridine dosage (0–5 mmol/kg) was adequate to control an otherwise normal clinical status, orotic acid excretion was still excessive (± 7 mmol/24 h). Urinary drug metabolites (uracil and uridine), however, accounted for less than 7% of the daily uridine dose, and no orotidine, or any abnormal pyri‐midines or purines, were identified at any time.2. Urinary uric acid excretion was high and plasma uric acid low, resulting in a clearance up to 4 times normal. This was attributed to the uricosuric effect of orotic acid.3. In direct contrast to previous findings in gouty subjects and healthy male controls we noted: (i) no increase in plasma or urinary uric acid levels, or uric acid clearance, following the change from a low to a high nucleoprotein regime (normally up to two‐fold); (ii) allopurinol reduced both urinary uric acid and total oxypurine levels by more than 50% on the low (normally unaffected) as well as the high (normally reduced 20–50%) nucleoprotein regime; (iii) a substantial (up to 70%) reduction in orotic acid excretion during allopurinol therapy (normally mild orotic aciduria), of similar magnitude and in parallel with the reduction in uric acid levels. Uric acid and orotic acid excretion were closely related throughout.These findings differ from those of a similar study of hereditary orotic aciduria and suggest there is competitive transport between exogenous (dietary) purines and pyrimidines, as well as an important interdependence between endogenous purine and pyrimidine metabolism, by mechanisms as yet undefined.
The effectiveness of digoxin‐specific F(ab‘)2‐antibody fragments in the treatment of digitoxin poisoning: experimental investigations in the cat
Authors: HESS T. , SCHOLTYSIK G. , RIESEN W. 
Published: March 2008

Abstract. In animal experiments heterologous digoxin‐specific F(ab')2 antibod fragments have been found to be effective for the treatment of arrhthmias induced b toxic doses of digoxin. So far the have been successfull emploed in three patients suffering from digoxin poisoning. The present stud was undertaken to test whether these antibodies are also effective in the treatment of digitoxin poisoning.Ventricular tachcardia, induced in digitalized cats b intravenous injections of digitoxin, was fatal in four out of five controls. However, sinus rhthm was reinstated in all the animals treated with digoxin‐specific F (ab') 2 after onset of the arrhthmia. Cross‐reactivit between the antibodies used and digitoxin, while slight in vitro, is, nevertheless, sufficient to justif their clinical use in cases of digitoxin poisoning.
Lipoprotein lipase in adipose tissue and plasma triglceride clearance in patients with primar hpertriglceridaemia
Authors: TALOR K. G. , HOLDSWORTH G. , GALTON D. J. 
Published: March 2008

Abstract.

The activit of lipoprotein lipase (E.C.3.1.1.3) extracted and released from adipose tissue has been measured in obese subjects with mild or severe hpertriglceridaemia. The Intralipid® tolerance test has been studied as a measure of in vivo clearance of exogenous triglceride from plasma.
Plasma triglceride clearance was reduced in patients with severe hpertriglceridaemia (> 4 mmol/1) and this was associated with reduced activities of extracted lipoprotein lipase in adipose tissue compared to patients with mild hpertriglceridaemia (2–4 mmol/1).
A course of insulin therap (20 u/da) for 1 week increased the extracted, but not the released component of the enzme from adipose tissue of hpertri‐glceridaemic patients.
Serum (25% v/v) potentiated the release of lipoprotein lipase from adipose tissue of normo‐ but not hpertriglceridaemic patients.
The effect of serum on enzme release was abolished if lipoprotein‐deficient serum was used. Addition of ver low densit lipoprotein (VLDL) or high densit liproprotein (HDL) restored the abilit of de‐lipidated serum to augment release of enzme from adipose tissue, but this was not observed with low densit lipoprotein (LDL).
It is suggested that a defect in the release of lipoprotein lipase activit in adipose tissue ma contribute to the development of hpertriglceridaemia in this group of patients.
The effect of antacids on the occurrence of bile acid and aspirin‐induced gastric lesions in rats
Authors: MORGAN R. J. , NELSON L. M. , RUSSELL R. I. , PLEVIN T. 
Published: March 2008

Abstract. Taurodeoxycholic acid increases the incidence of aspirin induced gastric bleeding in rats and in vitro is well bound by Aludrox (aluminium hydroxide) and poorly bound by Maalox (aluminium hydroxide and magnesium hydroxide). We studied the relevance of this binding, as demonstrated in vitro, by observing the effect of the antacids on the occurrence of taurodeoxycholic acid and aspirin‐induced bleeding in vivo in rats.Six groups of fasting male Sprague‐Dawley rats (n= 24) were intubated and given either water, Aludrox or Maalox and, 30 min later, aspirin or aspirin plus taurodeoxycholic acid. 4 h later the stomachs were examined and rats were scored positive if a lesion greater than 1 mm across was found (incidence of bleeding); a lesion scoring system was also used (severity of bleeding).The incidence of bleeding was increased from 63% with aspirin to 92% with aspirin plus taurodeoxycholic acid (P < 0.05). The incidence was reduced to 33% and 67% respectively by Aludrox and to 29% (P < 0.05) and 71% by Maalox. The severity of bleeding (median lesion score, quartiles in parentheses) was increased from 3 (l; 6.5) (aspirin) to 10.5 (6; 15) (aspirin plus taurodeoxycholic acid); P < 0.001. These were reduced to 0.5 (0; 3); P < 0.02 and 5 (05; 9‐5); P < 0.05 respectively by Aludrox and to 0 (0; 3); P < 0.02 and 3 (2;8); p < 0.02 by Maalox.The severity of bleeding was reduced by both antacids but the effect appeared to be mainly on the aspirin rather than the bile acid component of the damage.
Prostaglandin E2 in jejunal fluids and its potential diagnostic value for selecting patients with indomethacin‐sensitive diarrhoea
Authors: BUKHAVE K. , RASK‐MADSEN J. 
Published: March 2008

Abstract. Since prostaglandins (PGs) appear to be important in the pathogenesis of secretory diarrhoea, a radioimmunoassay for determination of PGE2 was applied to purified samples of jejunal fluids aspirated at the ligament of Treitz. Studies on validation of the assay system included quantification of PGE2 following alkali‐treatment of the samples, variation of the sample volume, and fractionation of immunoreactive‐and tracer PGE2. In addition, the specificity of the assay system was confirmed by gas chromatography‐mass spectrometry.In healthy volunteers (n= 22) the PGE2 concentration range was 5–205 pg/ml (99% confidence limits). Alcohol addicts (n= 27) with diarrhoea or steator‐rhoea had PGE2 levels within the normal range. Values beyond the 99% upper confidence limit were observed in ten out of seventeen patients with chronic diarrhoea (205–340 pg/ml) and two out of fifteen patients with intermittent diarrhoea (265 and 275 pg/ml) classified as irritable bowel syndrome. In six patients with high PGE2 concentrations indomethacin treatment (25 mg × 4 daily) halved the associated diarrhoea and reduced PGE2 concentrations to normal levels. Subsequently, a double‐blind multiple randomized clinical trial was carried out in two single patients. Indomethacin proved to be effective in preventing diarrhoea only in the patient with a raised PGE2 level (P< 0.005).
Multivariate analysis of clinical and biological data in cirrhotic patients: application to prognosis
Authors: EKINDJIAN O. G. , DEVANLAY M. , DUCHASSAING D. , LELUAN G. , KAMMERER J. , FOUET P. , AUGET J. L. , ACCARIO J. M. 
Published: March 2008

Abstract. One hundred and thirty‐one patients underwent clinical and biological investigations with the following determinations performed on the same day; presence or absence of ascites, icterus and/or encepha‐lopathy, coagulation study, biochemical determinations including albumin, transferrin and immuno‐globulins immunoassays. The principal component analysis of biological data showed two sets of highly representative and inversely correlated data; one included coagulation tests, albumin and transferrin, and the other included immunoglobulin A/transferrin ratio, immunoglobulin A and total bilirubin.Clinical and biological data were computed using discriminant analysis between dead and survivors. Six parameters were then selected (total bilirubin, ence‐phalopathy, factor V, AST, antithrombin III and transferrin) giving a correct prognosis in 81.6% (31 /38) of cases in a test sample. Neither ascites nor immuno‐globulins were useful for the estimation of the prognosis.
Cytophotometry of liver cells from ethanol‐fed rats: ethanol causes increased polyploidization and protein accumulation
Authors: GAUB J. , FAUERHOLDT L. , KEIDING S. , KONDRUP J. , PETERSEN P. , WANTZIN G. LANGE 
Published: March 2008

Abstract. Cellular protein and DNA content were determined by Feulgen‐Naphthol Yellow S cytophotometry on isolated liver cells from rats fed ethanol for 2–6 months. It was found that the parenchymal liver cells after ethanol feeding contained 13% more protein than cells of the same ploidy class from controls; that the average parenchymal cell in ethanol‐fed rats contained 16% more protein than in controls due to the increased occurrence of polypoloid cells; that the protein accumulation develops over 2 months, does not progress thereafter and disappears after a few days of reduced ethanol intake; that the tendency to form polyploid cells is accentuated during liver regeneration.It is suggested that the effect of alcohol on microtu‐bular function, which is regarded as the cause of the protein accumulation, may also bring about increased polyploidization.
Serum galactosylhydroxylysyl glucosyltransferase in acute myocardial infarction and during subsequent collagen scar formation
Authors: ANTTINEN HENRIK , JÄRVENSIVU PEKKA M. , SAVOLAINEN EEVA‐RIITTA 
Published: March 2008

Abstract. Changes in serum galactosylhydroxylysyl glucosyltransferase, an enzyme catalysing one of the intracellular post‐translational modifications in collagen biosynthesis, were studied in twenty‐four patients with acute myocardial infarction. The enzyme activity was monitored for 18 days from the onset of infarction, and at least a two‐peaked pattern was observed. The first peak corresponded to the stage of acute myocardial injury, there being a highly significant correlation between the maximal values for serum glucosyltransferase and a‐hydroxybutyrate dehydro‐genase. An average decrease in serum glucosyltransferase activity of 41% was noted during the following 24 h.A new gradual rise in serum glucosyltransferase activity, interpreted as indicating myocardial collagen scar formation, was observed 5 days after the onset of infarction, when the serum enzyme activities indicating myocardial injury had already declined. The average daily values for serum glucosyltransferase between 6 and 18 days correlated highly significantly with the maximal value for serum a‐hydroxybutyrate dehydro‐genase, which serves as a relative estimate of the size of the original myocardial infarction area. The data further suggest that certain other factors including heart failure and/or various drug treatments may also affect the magnitude of this second peak.
High density lipoprotein and other lipoproteins in normolipidaemic and hypertriglyceridaemic (type IV) men with coronary artery disease
Authors: MOBERG B. , WALLENTIN L. 
Published: March 2008

Abstract. The aim was to investigate whether a low concentration of high density lipoprotein (HDL) may be used as a risk indicator in normolipidaemic (n.l.) subjects, and whether a reduced HDL concentration constitutes an additional risk factor in hyperlipopro‐teinaemia. Eighty‐two men with angiographically documented coronary artery disease (CAD) were studied. The majority of the CAD men was either n.l. (n= 38) or had type IV hyperlipoproteinaemia (n= 22). These two groups were compared separately to one group of healthy n.l. subjects (n= 44), and one group of healthy subjects with type IV hyperlipoproteinaemia (n= 29).In about 50% of n.l. CAD men the HDL‐cholesterol (HDL‐C) was lower than the 15th percentile (0.90 mmol/1) of n.l. controls, and about 65% of n.l. CAD men had ratios of HDL‐C/total plasma cholesterol (C) lower than 0.17, the 15th percentile of n.l. controls. Almost all type IV subjects had reduced HDL‐C levels and decreased ratios of HDL‐C/C, whether they had obvious CAD or not. Thus, in normolipidaemia, but not in type IV hyperlipoproteinaemia, a low HDL‐C level may be used as an additional risk factor for CAD development.
Abnormal haem biosynthesis in chronic alcoholics
Authors: McCOLL KENNETH E. L. , MOORE MICHAEL R. , THOMPSON GEORGE G. , GOLDBERG ABRAHAM 
Published: March 2008

Abstract. The activities of six of the enzymes of haem biosynthesis have been examined in eleven chronic alcoholics admitted to hospital for alcohol withdrawal. The mitochondrial enzymes delta‐aminolae‐vulinic acid (ALA) synthase, coproporphyrinogen oxidase and ferrochelatase were monitored in peripheral leucocytes and the cytosolic enzymes ALA dehydratase, uroporphyrinogen‐1 ‐synthase and uro‐porphyrinogen decarboxylase in peripheral erythro‐cytes. Compared with control subjects the activity of the initial and rate controlling enzyme of the pathway, ALA synthase, was increased (P < 0.01) and the activities of ALA dehydratase and uroporphyrinogen decarboxylase depressed (P < 0.01, P < 0.02 respectively) on the day after admission but all returned to normal by the tenth to twentieth days after alcohol withdrawal. This stimulation of ALA synthase and inhibition of uroporphyrinogen decarboxylase explains the mechanism by which chronic alcohol ingestion may precipitate cutaneous hepatic porphyria.Two of the alcoholics were anaemic without evidence of haematinic deficiency and this was associated with depressed ferrochelatase activity and iron and porphyrin accumulation. The anaemia and related biochemical abnormalities in these two subjects were all corrected with alcohol withdrawal. It is proposed that inhibition of ferrochelatase activity is the biochemical basis of alcohol related sideroblastic anaemia.
Effects of weight reduction on plasma lipoproteins and adipose tissue metabolism in obese subjects
Authors: SORBRIS RALPH , PETERSSON BENGT‐GORAN , NILSSON‐EHLE PETER 
Published: March 2008

Abstract. The relationship between obesity and alterations in adipose tissue metabolism and lipid transport was studied in fourteen obese subjects before and after a weight reduction of 4–22 kg. Blood glucose and plasma insulin patterns after peroral glucose intake improved significantly, and plasma glucagon levels decreased markedly after treatment. Plasma trigly‐ceride and total cholesterol levels were not altered, but there was a 20% (P < 0.05) increase in HDL concentrations. Plasma free fatty acid and glycerol concentrations decreased, in parallel to a decrease in lipolysis rate, in vitro. Lipoprotein lipase and hepatic lipase activities in postheparin plasma, as well as the intravenous fat tolerance test, were normal and did not change significantly after weight loss. Lipoprotein lipase activity in adipose tissue, expressed per cell, was elevated and did not change after weight reduction. Also, the enzyme activity did not increase after glucose intake before or after treatment.The lack of effect on lipoprotein lipase activity and regulation in combination with significant improvements of other aspects of lipid and glucose transport is consistent with the view that alterations in LPL activity and regulation may represent an early and possibly primary defect in the development of obesity.
Regulation of biosynthesis of trypsinogen and chymotrypsinogen by nutritional and hormonal factors in the rat
Authors: STÖCKMANN F. , SÖLING H. D. 
Published: March 2008

Abstract. Experimental diabetes is associated with decreased pancreatic amylase activity resulting from reduced amylase synthesis and increased amounts of trypsinogen and chymotrypsinogen. The effects of different diets and of experimental diabetes on the synthesis of chymotrypsinogen and trypsinogen in rat pancreas were studied by measuring the incorporation of [4,5‐3H]leucine into these proteins by specific im‐munoprecipitation and simultaneous determination of the specific radioactivity of the pancreatic leucine pool. In addition the effect of acute glucagon treatment on the synthesis of these enzymes was examined. In rat pancreas two trypsinogens and one chymotrypsinogen were found. There was no precursor‐product relationship between the two trypsinogens. Changes in the rate of synthesis affected both isoenzymes to the same extent. Starvation was associated with a decreased rate of synthesis of total pancreatic protein, chymotrypsinogen and trypsinogen. A protein‐rich diet led to an increased rate of synthesis of chymotrypsinogen and trypsinogen, but not of total protein. A carbohydrate‐rich diet diminished the amounts of pancreatic chymotrypsinogen and trypsinogen and the rates of synthesis of these enzymes, whereas a fat‐rich diet had no significant effects on these parameters.Diabetes was associated with increased amounts of chymotrypsinogen and trypsinogen in the pancreas. This resulted from a dramatic increase in their rates of synthesis, whereas that of total pancreatic protein showed no significant change. The same pattern was observed in diabetic adrenalectomized rats or diabetic rats receiving the same amount of a standard diet as non‐diabetic controls. Treatment of rats with glucagon for 6 or 12 h led to a marked decrease of the amounts of pancreatic zymogens, whereas the rates of synthesis of chymotrypsinogen and trypsinogen were only slightly diminished.
Minor dietary effects on HDL in physically active men
Authors: KIENS B. , GAD P. , LITHELL H. , VESSBY B. 
Published: March 2008

Abstract. In a preceding prospective study an increased high‐density lipoprotein (HDL)‐cholesterol and apolipoprotein (apo) A‐I concentration occurred in healthy, non‐obese, initially sedentary men, aged 30–44 years, after 3 months of physical training. Dietary history data revealed an increase in the absolute amount of fat‐intake. In the present study we investigated whether a changed fat intake would influence the levels of lipoproteins, especially the HDL fraction, in twenty‐three regularly conditioning men, aged 30–44 years, with a maximal aerobic capacity of 53.4 ml/kg x min‐1± 0.8, mean ± SE. Ten subjects participated in an experimental group and thirteen in a control group. The experimental group studied before, after 4 weeks on a fat‐rich diet (fifty‐four energy‐% fat, twenty‐nine energy‐% carbohydrate) and after 4 weeks on a fat‐poor diet (twenty‐nine energy‐% fat, fiftythree energy‐% carbohydrate).The data reveal that these large dietary changes did not influence HDL‐cholesterol concentrations (1.71 ± O.10, 1.69± 0.12, 1.59± 0.13 mmol/l, mean ± SE, during ordinary, fat‐rich and fat‐poor diet, respectively) and only influenced apo A‐I levels to a minor degree after the fat‐poor diet (1 34 ± 6.1, 134f7.1 and 123 ± 4.7 arbitrary units, mean values ± SE) during ordinary, fat‐rich and fat‐poor diet, respectively). No changes were observed in the controls before and after 8 weeks. During the study training habits and body weight were constant.These findings show that large variations in the intake of dietary neutral fat only to a minor extent influence the level of HDL‐cholestrerol and apo A‐I in physically active subjects.
Adenylate cyclase activity and cAMP content of human platelets in uraemia
Authors: VLACHOYANNIS J. , SCHOEPPE W. 
Published: March 2008

Abstract. We investigated the effects of uraemia and haemodialysis on the basal activity of adenylate cyclase and the cyclic‐AMP content of human platelets in patients with end‐stage renal insufficiency, patients receiving maintenance haemodialysis, and as controls healthy voluntary subjects.Basal adenylate cyclase activity in terminal renal disease (creatinine clearance less than 15 ml/min/1·73 m2) was 824 ± SEM 57, in comparison to the healthy subjects with 453 ± SEM 28 (P< 0·001). We also found significant elevation (P< 0·001) of platelet cAMP levels as compared to the controls. Basal adenylate cyclase activity and platelet cAMP levels were approximately normal in the dialysed patients.These results show that uraemic toxins adversely affect the platelet AC‐cAMP system, possibly causing impaired platelet aggregation and the bleeding diathesis of uraemia.