bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of puromycin on subepithelial deposits induced by antibodies directed against tubular antigens: a quantitative study*
Authors: BERTANI T. , NOLIN L. , FOIDART J. , VANDEWALLE A. , VERROUST P.
Published: March 2008

Abstract. The mechanism of the GN induced by the intravenous injection of antibodies directed against renal tubular epithelial antigens (RTE) was studied by the use of antibody specifically purified by affinity chromatography. With this reagent RTE antigens could be demonstrated on frozen sections of glomeruli as well as on glomerular cells in culture. The antibodies were radiolabelled, and using paired label techniques glomerular binding could be measured in vivo. In normal rats, approximately 4% of the antibody injected was specifically bound in the glomeruli. Binding was not detectable on proximal tubular brush borders. In rats treated with 100 mg/kg of aminonucleoside of puromycin, a substance known to induce alterations of glomerular epithelial cells, it could be shown that glomerular binding was selectively decreased. These observations indicate that immune deposits in passive Heyman nephitis are formed mainly in situ and that local alteration of the glomerulus can markedly influence deposit formation.
Cardiovascular and adrenergic effects of cigarette smoking during immediate non‐selective and selective beta adrenoceptor blockade in humans
Authors: TRAP‐JENSEN JENS , CARLSEN JAN E. , SVENDSEN TAGE LYSBO , CHRISTENSEN NIELS JUEL
Published: March 2008

Abstract. The cardiovascular and adrenergic responses to cigarette smoking during acute selective and non‐selective beta adrenoceptor blockade were studied in seven young healthy volunteers in a double blind cross‐over fashion. Heart rate, arterial blood pressure, forearm blood flow and plasma levels of adrenaline and noradrenaline were determined before and during the terminal 5 min period of 15 min smoking test.

During smoking, plasma concentrations of adrenaline increased markedly and evenly by approximately 0.3 ng/ml in all three experimental sessions. Plasma concentrations of noradrenaline remained unchanged.

Propranolol, a non‐selective beta blocker, caused a marked rise in diastolic and mean blood pressure and forearm vascular resistance during smoking. This response was not seen in the control series or after selective beta‐1 blockade with atenolol. This difference is attributable to propranolol's blockade of adrenaline's vasodilating effect mediated by beta‐2 receptors in the resistance vessels. Furthermore, atenolol attenuated the systolic blood pressure and tachycardiac responses induced by cigarette smoking by comparison with placebo.

This study suggests that selective beta‐1 blockers are preferable in the management of patients who are habitual smokers.
Biliary lipid composition during treatment with different hypolipidaemic drugs*
Authors: ANGELIN BO , EINARSSON KURT , LEIJD BARBRO
Published: March 2008

Abstract. In an attempt to clarify the possible lithogenic effects of commonly used hypolipidaemic drugs, gallbladder bile was obtained from patients with primary hyperlipoproteinaemia before and during treatment with nicotinic acid (n= 13), cholestyramine (n= 19), clofibrate (n= 11), and a combination of cholestyramine and clofibrate (n= 11). Each treatment period was minimum 6 weeks, and standardized dietary conditions were obtained.

Both nicotinic acid and clofibrate treatment caused an increase in biliary cholesterol concentration relative to biliary total lipids (bile acids, phospholipids, and cholesterol). During cholestyramine medication the relative cholesterol concentration fell. A combination of cholestyramine with clofibrate medication led to a decrease of bile saturation to pretreatment levels in nine of the eleven subjects. In the other two a further increase in the cholesterol saturation of the bile occurred.

Treatment with nicotinic acid and clofibrate but not with cholestyramine is thus probably associated with an increased risk for development of cholesterol gallstones. It is suggested that addition of cholestyramine may be a possible way to prevent the lithogenic effect of clofibrate in patients with hyperlipoproteinaemia when not only hypocholesterolaemic but also hypotriglyceridaemic effects are wanted.
Increased biosynthesis of thromboxane A2 by diabetic platelets
Authors: ZIBOH VINCENT A. , MARUTA HIROYUKI , LORD JONATHAN , CAGLE WILLIAM D. , LUCKY WILLIAM
Published: March 2008

Abstract. Because ADP has been reported to produce a secondary wave of platelet aggregation in diabetic subjects, and since ADP is known to enhance normal platelet biosynthesis of pro‐aggregating thromboxane A2, we tested whether or not the reported increased sensitivity of diabetic platelets to ADP may also result in increased platelet biosynthesis of thromboxane A2. To test this hypothesis, 14C‐arachidonic acid (14C‐AA) was incubated in vitro with washed human platelets' in the presence or absence of ADP. These studies included platelets isolated from thirty normal volunteers, twenty‐six diabetic subjects with and without known vascular complications, eighteen non‐diabetic pregnant females and fourteen pregnancy‐induced diabetic females. Data from these studies demonstrated: (i) a significant increase in the capability of diabetic platelets in response to ADP to biosynthesize thromboxane A2 from arachidonic acid when compared to platelets from normal controls (P < 0.001); (ii) a significant increase in thromboxane A2 biosynthesis by platelets from pregnancy‐induced diabetic subjects over nondiabetic pregnant females (P < 0.001); (iii) a two‐fold increase in thromboxane A2 biosynthesis by platelets from diabetic subjects with vascular complications when compared to those without vascular complications. Although our data also showed approximately a twofold increase in thromboxane A2 biosynthesis by platelets from diabetic subjects with greater than 10 years of the disease when compared to diabetic subjects with less than 10 years, these latter results were, however, not statistically significant. Results from these studies suggest that a relationship may exist between the markedly increased ADP‐induced platelet aggregation in diabetes mellitus and the vascular complications associated with this disease. Whether or not increased capacity of the diabetic platelet to biosynthesize pro‐aggregating thromboxane A2 in response to ADP or other pro‐aggregating agents is per se a triggering factor in occlusive vascular diseases reported in diabetic subjects must await further studies.
Renal excretion of proteins and enzymes in workers exposed to cadmium
Authors: BERNARD A. , BUCHET J. P. , ROELS H. , MASSON P. , LAUWERYS R.
Published: March 2008

Abstract. The proteinuria rate and the relative clearances of β2‐microglobulin, orosomucoid, albumin, transferrin and IgG were measured in forty‐two workers exposed to cadmium and in seventy‐seven control workers. A tubular type proteinuria with an increased excretion of β2‐microglobulin and often also a glomerular type proteinuria with an increased excretion of orosomucoid, albumin, transferrin and IgG were observed mainly in workers exposed to cadmium for more than 25 years and whose cadmium concentration in blood exceeded 1 μg Cd/100 ml and that in urine 10 μg Cd/g creatinine. The glomerular dysfunction was also suggested by an increased plasma level of β2‐microglobulin and creatinine. Both tubular and glomerular impairments occurred with the same prevalence and were not necessarily associated. The increased release of β‐galactosidase by the kidney suggested that cadmium can damage some epithelial cells.
Partial deficiency of hypoxanthine‐phosphoribosyltransferase:evidence for a structural mutation in a patient with gout
Authors: GUTENSOHN W. , JAHN H.
Published: March 2008

Abstract. A mutant hypoxanthine‐phosphoribosyltransferase (EC 2.4.2.8) from a patient with gout is examined. The activity of the erythrocyte enzyme is about 5% of normal in this case. Immunoprecipitation studies using antiserum against highly purified human hypoxanthine‐phosphoribosyltransferase reveal that the patient's erythrocytes contain a normal amount of cross‐reacting material. The mutant enzyme has an altered net charge as shown by preparative isoelectric focusing (pI values of 5.75 and 4.55). The influence of chemical modification on enzymic activity was studied using a number of different reagents directed against sulfhydryl‐, amino‐, and guanidino‐groups. Compared with normal hypoxanthine‐phosphoribosyltransferase the mutant enzyme shows a generally lowered susceptibility to active site‐directed inhibition. It is concluded that the patient's enzyme is the product of a structural mutation.
Quantitation of 3‐ethyl‐5‐hydroxy‐4,5‐dimethyl‐Δ3‐pyrrolin‐2‐one in the urine of patients with acute intermittent porphyria
Authors: GRAHAM D. J. M. , BRODIE M. J. , McCOLL K. E. L. , MOORE M. R. , GOLDBERG A.
Published: March 2008

Abstract. The monopyrrole 3‐ethyl‐5‐hydroxy‐4,5‐dimethyl‐Δ3‐pyrrolin‐2‐one (hydroxyhaemopyrrolin‐2‐one) has been quantitated in the urine of eight patients with acute intermittent porphyria in attack or remission and ten subjects latent for the disorder. Previous qualitative investigations had revealed an association between hydroxyhaemopyrrolin‐2‐one excretion and certain psychiatric disorders including acute porphyria.

Urinary excretion of hydroxyhaemopyrrolin‐2‐one was significantly elevated in patients with acute intermittent porphyria in attack or remission and in latent subjects. No significant difference could be found between the excretion in attack or remission and latency.

A significant association was found in all subjects between urinary hydroxyhaemopyrrolin‐2‐one concentrations and the urinary excretion of the porphyrin precursors δ‐aminolaevulinic acid and porphobilinogen. There was also found to be a linear relationship between the excretion of δ‐aminolaevulinic acid and of porphobilinogen.

Excretion of hydroxyhaemopyrrolin‐2‐one, δ‐aminolaevulinic acid and porphobilinogen was also followed in one subject throughout the duration of an acute attack.

The significance of the findings are discussed in relationship to a possible role of hydroxyhaemopyrrolin‐2‐one in the manifestations of acute porphyria.
Reversible abnormalities of low density lipoprotein composition in familial hypercholesterolaemia
Authors: JADHAV A. V. , THOMPSON G. R.
Published: March 2008

Abstract. Low density lipoprotein (LDL) composition was analysed in twenty‐one patients with familial hypercholesterolaemia, including six homozygotes. By comparison with nineteen controls the patients' LDL had an increased ratio of cholesterol:phospholipid and a decreased ratio of lecithin:sphingomyelin; these changes were more marked in homozygotes than in heterozygotes. Treatment of seven patients with plasma exchange temporarily resulted in near‐normalization of the composition of their LDL. These results suggest that abnormalities of LDL composition in familial hypercholesterolaemia are secondary to hypocatabolism of LDL, which prolongs the half‐life of LDL and thus increases the mean age of the population of particles circulating in plasma.
Renin, aldosterone and renal haemodynamics in cirrhosis with ascites
Authors: ARROYO VICENTE , BOSCH JAUME , MAURI MONTSE , VIVER JOSEP , MAS ANTONI , RIVERA FRANCISCA , RODES JOAN
Published: March 2008

Abstract. The interrelationships between the reninangiotensin‐aldosterone system, renal haemodynamics and urinary sodium excretion were investigated in fifty‐six non‐azotaemic cirrhotics with ascites. In twelve additional patients the renal renin secretion rate was also studied. Plasma renin activity and concentration and plasma aldosterone ranged from normal to very high values. There was a significant inverse relationship between plasma aldosterone and the urinary sodium excretion. Plasma aldosterone showed a highly significant direct correlation with plasma renin activity, and plasma renin concentration was closely and directly related to the estimated renin secretion rate. Neither plasma renin activity, plasma renin concentration nor the estimated renin secretion rate correlated with the renal plasma flow or the glomerular filtration rate. These results suggest that in non‐azotaemic cirrhosis with ascites the renin‐angiotensin‐aldosterone system is an important factor influencing sodium excretion, increased plasma renin and aldosterone concentrations are mainly due to an increased secretion rate, and total renal perfusion is not a major factor influencing renin secretion.
A clinical and immunopathological study of 304 cases of glomerulonephritis in Tunisia
Authors: VERROUST P. , BEN‐MAIZ H. , MOREL‐MAROGER L. , MAHFOUD A. , GENITEAU M. , BENAYED H. , RICHET G.
Published: March 2008

Abstract. 304 cases of glomerulonephritis were biopsied in Tunisia and studied morphologically. The incidence of glomerulonephritis with marked proliferation of endocapillary cells was 60%, a figure considerably higher than in other large series. Using a Clq binding assay, statistically significant levels of immune complexes were found in cases of acute proliferative glomerulonephritis. Amongst other types of glomerulonephritis, circulating immune complexes were frequently found in systemic lupus erythematosus but only in a low percentage of primary glomerulonephritis with or without immunoglobulin deposits.
Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease
Authors: KUUTTI‐SAVOLAINEN EEVA‐RIITTA , RISTELI JUHA , MIETTINEN TATU A. , KIVIRIKKO KARI I.
Published: March 2008

Abstract. Serum immunoreactive prolyl hydroxylase protein was measured in sixty‐five patients with liver disease, and liver prolyl hydroxylase activity, immunoreactive prolyl hydroxylase protein and collagen hydroxyproline in forty of these patients. Serum immunoreactive prolyl hydroxylase protein was above the 95% confidence limit of the controls in most patients with primary biliary cirrhosis, portal cirrhosis, acute hepatitis and cancer with liver metastases, but below this in most patients with fatty liver, chronic active hepatitis, extrahepatic cholestasis, cholangitis, cancer without liver metastases and other malignant diseases. Elevated serum immunoreactive prolyl hydroxylase protein decreased rapidly with time in acute hepatitis but not in primary biliary cirrhosis. Liver prolyl hydroxylase activity and immunoreactive prolyl hydroxylase protein were elevated in the same diseases as serum immunoreactive prolyl hydroxylase protein, and correlated significantly with the latter whereas no correlation was found between serum immunoreactive prolyl hydroxylase protein and collagen hydroxyproline. Serum immunoreactive prolyl hydroxylase protein correlated highly significantly with serum alkaline phosphatase and weakly with serum aspartate aminotransferase in primary biliary cirrhosis, but not in any other disease. No correlation was found between serum immunoreactive prolyl hydroxylase protein and other tests of liver function. The results suggest that changes in serum immunoreactive prolyl hydroxylase protein in liver disease primarily reflect changes in this enzyme in the hepatic tissue, and that assays of serum immunoreactive prolyl hydroxylase in liver disease may give useful information on the actual hepatic collagen synthesis.
Chronic administration of chenodeoxycholic acid increases cholesterol saturation in bile in the dog
Authors: POUPON R. E. , POUPON R. Y. , DUVAL M. , QUERNEC L. LE , ERLINGER S.
Published: March 2008

Abstract. Six dogs were given chenodeoxycholic acid, 200 mg/day for 15 days; gallbladder and hepatic bile samples were taken and biliary bile acids, phospholipids and cholesterol were compared to those of fourteen control dogs. It was found that: (1) the cholesterol saturation index of gallbladder bile was higher in treated dogs (0.12 ± 0.06; m ± SD) than in controls (0.07 ± 0.01; P < 0.05); the proportion of chenodeoxycholic acid in gallbladder bile was higher in treated dogs (27.8 ± 12.5%) than in controls (4.5 ± 1.9%; P < 0.01); (2) in hepatic bile, the saturation index and proportion of chenodeoxycholic acid were significantly higher in treated dogs (respectively 0.13 ± 0.03 and 21.6 ± 8.8%) than in control dogs (respectively 0.07 ± 0.01; P < 0.01 and 4.6 ± 2.2%; P < 0.01). In the dog, chronic administration of chenodeoxycholic acid increases cholesterol saturation in bile. It is concluded that the difference of effect of chenodeoxycholic acid in man and in the dog is not related to the duration of administration, but to a species difference.
Pituitary hormones and the small bowel: effect of hypophysectomy on intestinal adaptation to small bowel resection in the rat*
Authors: TAYLOR BRYCE , MURPHY GERARD M. , DOWLING R. HERMON
Published: March 2008

Abstract. The influence of pituitary hormones on intestinal adaptation to small bowel resection was studied by examining jejunal and ileal structure and function in control and in sham‐operated rats, and in animals with 50% proximal or distal resection which were divided into three main groups: normally‐fed, hypophysectomized, and pair‐fed. The pituitary was removed 2 weeks before intestinal surgery and gut structure and function were studied 4 weeks later. The effectiveness of hypophysectomy was confirmed by histological examination of the aspirated pituitary, and by showing a significant subsequent reduction in weight of the testes and adrenals. Food intake and body weight fell significantly after removing the pituitary; intestinal surgery caused a transient further decrease in food intake.

Measurements of intestinal villus height and crypt depth, indices of mucosal mass (mucosal wet weight, protein and DNA content/cm intestine), measurements of mucosal a‐glucosidase activity, and in vivo galactose absorption/unit length of intestine all showed comparable results. In rats with an intact intestine, resection resulted in mucosal hyperplasia and increased segmental absorption. Following hypophysectomy, there was marked mucosal hypoplasia and hypofunction which seemed to be due largely to associated hypophagia since comparable changes were found in the pair‐fed, sham‐operated rats. However following pituitary removal, both distal jejunum and proximal ileum retained their capacity to regenerate though the magnitude of this adaptive change was much greater in the resected, pair‐fed rats suggesting that hypophagia alone cannot explain the diminished adaptation to resection after hypophysectomy. By inference, pituitary hormones do influence the adaptive response to resection.
Impaired feedback control of fat induced gastric inhibitory polypeptide (GIP) secretion by insulin in obesity and glucose intolerance
Authors: EBERT R. , FRERICHS H. , CREUTZFELDT W.
Published: March 2008

Abstract. To investigate the role of endogenous insulin on the secretion of immunoreactive gastric inhibitory polypeptide (IR‐GIP) the response of IR‐GIP and immunoreactive insulin (IRI) to an oral fat load (100 g triglyceride) alone and during an intravenous glucose infusion (0.7 g/kg/h) was examined in normal weight and obese subjects. In normal weight subjects the fat induced integrated rise of IR‐GIP was 112.7 ± 9.4 ng/ml/120 min. When glucose and fat were given together this IR‐GIP response was lowered to 46.2 ± 2.9 ng/ml/120 min while the serum IRI response to i.v. glucose and the glucose tolerance were enhanced by fat ingestion. In obese subjects with normal glucose tolerance the GIP suppressing effect of i.v. glucose infusion was less marked than in controls. The integrated IR‐GIP response to fat ingestion was 225.6 ± 20.3 ng/ml/120 min and to fat plus glucose 152.6 ± 14.8 ng/ml/120 min. In obese subjects with glucose intolerance i.v. glucose completely failed to lower the exaggerated secretion of IR‐GIP following oral fat. Thus, a graded abnormality of the GIP response to glucose induced insulin release occurs in obesity with normal and pathological glucose tolerance. After reducing the ideal body weight of six obese subjects with glucose intolerance by hypocaloric diet for 3 weeks the exaggerated rise of IR‐GIP after oral fat was reversed and the lowering effect of i.v. glucose on the IR‐GIP response re‐established.
Inhibition of gastrin secretion by hypertonic solutions in patients with pernicious anaemia and duodenal ulcer
Authors: BRANDSBORG M. , LøVGREEN N. A. , BRANDSBORG O. , CHRISTENSEN N. J.
Published: March 2008

Abstract. Serum gastrin increased in patients with pernicious anaemia after a beef‐meal, but decreased after an oral load of glucose, xylose or sodium chloride. 50 g of glucose and 25 or 75 g of xylose suppressed serum gastrin to appoximately 40% of basal values at 60 min and were slightly more effective than 10 g of sodium chloride.

There was no rise in beef‐meal stimulated serum gastrin concentration in vagotomized patients and only a slight rise in two patients with duodenal ulcer when an oral dose of 10 g of sodium chloride was given together with the beef‐meal. 25 g of xylose suppressed basal serum gastrin concentration significantly in six vagotomized patients.

Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in all subjects examined. Further studies indicated, however, that vasopressin was only effective when pharmacological plasma concentrations were attained.

The inhibitory effects of 10 g of glucose given orally and intraduodenally were compared in six patients with pernicious anaemia. Serum gastrin concentration decreased approximately to the same extent in both experiments.

It is concluded that the inhibitory effect of glucose on gastrin secretion most likely is mediated hormonally via osmo‐receptors located in the small intestine.
Effect of hyperglycaemia‐induced hyperosmolality on heart function in the dog
Authors: POGÁTSA GÁBOR , DUBECZ ERZSÉBET
Published: March 2008

Abstract. Changes in myocardial water content, left ventricular diastolic stiffness, cardiac performance, coronary blood flow, myocardial contractile force, rate of change of myocardial force, and peak acceleration of the aortic volume flow were examined in twenty‐five dogs during glucose‐induced hyperosmolality before and after pancreatectomy, the latter with and without insulin treatment. Glucose‐induced hyperosmolality accounted for myocardial dehydration, increased diastolic stiffness and consequent decrease of left ventricular performance only in the absence of insulin, while coronary blood flow, myocardial contractile force, rate of change of myocardial force and peak acceleration of the aortic volume flow increased independently from the presence or absence of insulin during the glucose‐induced hyperosmolality. These findings suggest that the frequent development of heart failure in hyperosmolar diabetic coma could partly be explained by myocardial dehydration and by the consequent decrease in left ventricular compliance and performance.
Differential effects of fibroblast and leucocyte interferon in HBsAg positive chronic active hepatitis
Authors: WEIMAR W. , HEIJTINK R. A. , SCHALM S. W. , SCHELLEKENS H.
Published: March 2008

Abstract. Six patients with hepatitis B surface antigen, hepatitis B ‘e’ antigen positive chronic active hepatitis, and elevated hepatitis B specific DNA polymerase activity were treated sequentially with fibroblast and leucocyte interferon. Fibroblast interferon induced a fall in serum transaminase activities in all patients, whereas a consistent decline in DNA polymerase activity was observed during leucocyte interferon administration only. After treatment one patient remained persistently DNA polymerase and hepatitis B ‘e’ antigen negative, whereas relapse to initial values occurred in others. Side effects included severe but reversible granulocytopenia, and chills responding to promethazine treatment. The differential biological activity of fibroblast and leucocyte interferon in our patients coincides with their non‐identity in in vitro studies.
Effects of weight reduction on squalene, methyl sterols and cholesterol and on their synthesis in human adipose tissue
Authors: TILVIS R. , MIETTINEN T. A.
Published: March 2008

Abstract. Quantitation of cholesterol and its precursors from human adipose tissue biopsies revealed very high squalene and moderately high methyl sterol concentrations. The squalene and cholesterol values were correlated with each other. Weight reduction in obese subjects following a jejuno‐ileal bypass resulted in a significant but transient increase in adipose tissue cholesterol. The squalene concentration was also increased post‐operatively, the maximum being reached about 6 months later than that of cholesterol as if the mobilization of squalene from shrunken adipocytes had been slow. Weight reduction with a 2–14 day total fast significantly reduced the adipocyte size but had no consistent effect on adipose tissue squalene, methyl sterol and cholesterol concentrations or on their adipocyte contents. Incubation of adipose tissue with labelled acetate and mevalonate revealed that the bulk of the labels in non‐saponifiable lipids stayed in the large intermediate pools of methyl sterols and squalene in particular, fairly little being found in the cholesterol fraction itself. The total fast inhibited the incorporation of both 14C‐acetate and 3H‐mevalonate to squalene, methyl sterols and cholesterol, suggesting that cholesterol synthesis was inhibited before and after the mevalonate step.
Beneficial effects of colchicine in experimental nephrotoxic serum nephritis in the rat
Authors: PENCHAS S. , CHARUZI I. , BOSS J. H.
Published: March 2008

Abstract. Glomerulonephritis was induced in rats by multiple injections of rabbit anti‐rat kidney serum. Colchicine was administered daily for 4 months to nephrotoxic serum treated rats and untreated control animals. Nephritic rats receiving colchicine had significantly less proteinuria and less glomerular damage than unprotected nephritic animals. A possible role for colchicine in the early treatment of human glomerulonephritis is suggested.
The effect of biliary diversion on mucosal enzyme activity and brush border glycoprotein degradation in rats with self‐filling blind loops
Authors: JONAS ANITA , FORSTNER GORDON
Published: March 2008

Abstract. The significance of unconjugated bile salts in the development of mucosal lesions in the contaminated bowel syndrome was investigated by preparing jejunal self‐filling blind loops in rats in which pancreatic and biliary flow had been diverted to the mid ileum. Findings in these animals were compared with those in non‐operated controls, controls with the bile diversion procedure alone, and rats with self‐filling blind loops but unaltered biliary flow. Surface damage was monitored by determining relative glycoprotein degradation (3H/14C) ratios with the radioactive precursor D‐glucosamine, and measuring disaccharidase activities in mucosal homogenates and isolated brush border membranes. Data was analysed from the blind loop and segments above and below it, and compared with the corresponding upper, middle and lower segments of control rats. The blind loop, middle and upper intestinal segments of the rats with diverted bile flow contained no measurable bile salts. All rats with surgical procedures developed significant steatorrhoea. Fat excretion was greatest in the rats with the blind loop plus bile diversion. In rats with blind loops decreased conjugated:free bile salt ratios were found in all segments which contained bile, indicating excessive bacterial deconjugase activity. Disaccharidase activities were significantly reduced compared with control segments in homogenate and brush border fractions from self‐filling blind loops with and without bile salts. There was no difference between values in the two types of blind loop. Brush border glycoprotein degradation in the blind loops was significantly increased, to the same extent in both types of blind loop, but blind loop homogenate glycoprotein degradation was not altered indicating that degradation was specifically increased in the surface membrane. Blind loop disaccharidase activity in bile‐diverted animals was decreased out of proportion to changes in upper and lower segments and therefore was specifically related to the area of greatest bacterial overgrowth. These results indicate that factors other than bile salt deconjugation play a part in the pathogenesis of mucosal injury in the bacterially contaminated bowel.
Metabolism of endogenous plasma triglyceride in familial hypercholesterolaemia: studies of affected and unaffected siblings of two kindreds
Authors: ANGELIN BO
Published: March 2008

Abstract. Plasma endogenous triglyceride kinetics were investigated using [3H]glycerol in five unaffected and eight affected (heterozygous) siblings of two kindreds with familial hypercholesterolaemia. No consistent differences between affected and unaffected siblings regarding plasma triglyceride levels or apparent triglyceride production rates as determined over 10 h were seen, and the values observed were generally within the ranges seen in twelve normolipidaemic controls. It is concluded that abnormal plasma triglyceride metabolism is not a feature of heterozygous familial hypercholesterolaemia.
Phytosterolaemia, xanthomatosis and premature atherosclerotic arterial disease: a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis
Authors: MIETTINEN TATU A.
Published: March 2008

Abstract. A fourth case is described in which phytosterolaemia, earlier diagnosed as familial hypercholes‐terolaemia, was associated with normocholesterol‐aemia, hypersplenism and premature atherosclerotic arterial disease requiring a three‐vessel coronary bypass at the age of 29 years. During a follow‐up of 5 years 22–26% and 27–30% of serum and bile sterols were plant sterols, respectively. In addition to campes‐terol and β‐sitosterol, stigmasterol and a fourth major plant sterol, tentatively identified as avenasterol, were found in bile, and in free and esterified forms in all serum lipoproteins. Analysis of faecal steroids and measurement of biliary lipid secretion indicated that in addition to enhanced absorption of plant sterols their decreased biliary secretion contributed to the development of phytosterolaemia. Impaired biliary cholesterol secretion was compensated for by a markedly reduced cholesterol but normal bile acid synthesis and resulted in bile undersaturated with respect to cholesterol, in a reduced intestinal cholesterol pool and in a very low faecal excretion of cholesterol as neutral sterols. Cholestyramine brought about a modest increase in cholesterol elimination as bile acids, increased cholesterol synthesis as evidenced by the sterol balance value and the increased cholesterol precursors squalene and methyl sterols in plasma and bile, and reduced the plasma cholesterol by 21% and plant sterols by 16%, but had no effect on the biliary composition of main sterols.
Insulin and glucose uptake and insulin sensitivity in patients with peripheral arterial insufficiency
Authors: HAMMARSTEN JAN , HOLM GÖRAN , HOLM JAN , SCHERSTÉN TORE
Published: March 2008

Abstract. There have been previous reports of evidence for increased insulin sensitivity in patients with intermittent claudication as the only symptom of arterial insufficiency. This study was designed to evaluate the role of peripheral tissue with respect to insulin sensitivity in such patients. Intravenous glucose tolerance tests (IVGTT) and intravenous insulin tolerance tests (IVITT) were performed in patients with peripheral arterial insufficiency and in controls. During IVGTT the plasma insulin values were significantly lower in patients with arterial insufficiency. During IVITT the venous concentration of glucose decreased more and the area over the glucose curve was significantly larger, suggesting a higher insulin sensitivity in this group. The low insulin values could not be referred to a larger distribution volume or an increased degradation rate, suggesting decreased pancreatic insulin release in this group. At the time of surgery for arterial insufficiency and for varicose veins in controls, the uptake of insulin and glucose and the release of lactate were measured over the leg before and after a glucose load. The uptake of insulin over the leg correlated positively with the arterial insulin concentration and the uptake of glucose in both groups. The insulin uptake had a tendency to be increased in legs with arterial insufficiency during the glucose challenge. The glucose uptake in the leg did not differ in the basal state, but was 3 times higher in the legs of patients with arterial insufficiency during glucose challenge. The increased glucose uptake in this group could be ascribed to a high insulin sensitivity in the leg, as defined by glucose uptake per unit of insulin taken up.
Haemostatic effects of lysine vasopressin and triglycyl lysine vasopressin infusion in patients with cirrhosis
Authors: PROWSEy C. V. , DOUGLAS J. G. , FORREST J. A. H. , FORSLING M. L.
Published: March 2008

Abstract. Eight patients with cirrhosis were infused with lysine vasopressin (10 ng LVP) and triglycyl lysine vasopressin (750 μg and 2000 fig Glypressin, GVP) on separate occasions. LVP infusion resulted in an increase in factor VIII, factor VHI‐related antigen and plasminogen activator (PA). The factor VIII antigen: activity ratio decreased following infusion, but factor VIII electrophoretic mobility and in vitro decay rate were unchanged.

GVP infusion produced no change in factor VIII or PA. Assay of vasopressin‐like antigen and antidiuretic activity showed that GVP is cleaved to LVP in vivo. The low levels of LVP formed by this reaction might explain the prolonged vasometer effects of GVP, as well as its inability to cause release of factor VIII or PA.
The effect of ethynyl oestradiol on biliary lipid composition in young men
Authors: ANDERSON A. , JAMES O. F. W. , MACDONALD H. S. , SNOWBALL S. , TAYLOR W.
Published: March 2008

Abstract. A daily oral dose of 30 μg of ethynyl oestradiol was taken for 7 days by thirteen healthy young men. Bile was obtained by duodenal aspiration before and after treatment. The cholesterol saturation index of the bile was significantly greater after treatment due to an increase in the molar percentage of cholesterol and phospholipid and a decrease in the molar percentage of total bile acids. The oestrogen had no effect on cholic, deoxycholic and chenodeoxycholic acids expressed as a percentage of the total bile acids, and no change occurred in serum cholesterol. However, there was a significant decrease in serum testosterone concentration at the end of the treatment.
Plasma cyclic nucleotide responses to insulin‐induced hypoglycaemia and methacholine in patients with hyperthyroidism
Authors: OKADA FUMIHIKO , IDE HAJIME , HATA SHUNICHI , HONMA MIYUKI , UI MICHIO
Published: March 2008

Abstract. The effect of insulin‐induced hypoglycaemia and methacholine on plasma cAMP and cGMP levels was studied in normal volunteers, hyperthyroid and hypothyroid patients. A significant positive correlation existed between the maximal increase in plasma cAMP and the maximal decrease in plasma glucose in normals during insulin‐induced hypoglycaemia. Therefore, the plasma cAMP response is considered to be dependent on the degree of hypoglycaemia, rather than the dose of insulin. The cAMP response to hypoglycaemia was significantly higher in hyperthyroid patient, and was lower in patients with hypothyroidism than in normals. The cAMP response of the hyperthyroid patients was normalized when their hyperthyroidism was controlled after 3 months of treatment. The plasma level of cGMP was slightly elevated during hypoglycaemia, but there was no significant difference between controls and hyperthyroid patients. The cGMP response to methacholine, which is probably mediated by cholinergic receptors, was significantly potentiated in hyperthyroid patients. The cAMP response, which is presumably dependent on endogenous catecholamines secreted during metha‐choline‐induced hypotension, was also enhanced in hyperthyroid patients. It is likely that β‐adrenergic receptor responses and cholinergic receptor responses are both enhanced in hyperthyroidism.
In vivo and in vitro effects of adrenaline on conversion of thyroxine to triiodothyronine and to reverse‐triiodothyronine in dog liver and heart
Authors: NAUMAN A. , KAMIŃSKI T. , HERBACZYŃSKA‐CEDRO K.
Published: March 2008

Abstract. Infusion of adrenaline in healthy dogs in a dose simulating spontaneous release of the catecholamine during experimental myocardial infarction produced a significant decrease in the conversion of thyroxine (T4) to triiodothyronine (T3) and a moderate increase in the conversion of T4 to reverse‐triiodothyronine (rT3). Similar changes in deiodination of T4 to T3 and to rT3 were also observed when adrenaline was added in vitro to liver and heart homo‐genates. These results are consistent with a direct effect of adrenaline on T4 deiodination as degradation of exogenous T4, T3 and rT3 was only slightly increased under the experimental condition employed. The present study suggests that increased tissue exposure to adrenaline might contribute to the hormonal changes seen in at least some cases of the Mow T3 syndrome'.
Regulation of sterol synthesis in human intestinal mucosa
Authors: BETTERIDGE D. J. , KRONE W. , MIDDLETON CAROLE , GALTON D. J.
Published: March 2008

Abstract. The effect of dietary factors and experimental manipulations designed to perturb the entero‐hepatic circulation on the rate of sterol synthesis were studied in freshly isolated human jejunal mucosa from normal subjects.

Fasting significantly reduced the rate of sterol synthesis from [14C] acetate in jejunal mucosa obtained from normolipaemic obese subjects. A high cholesterol diet had no consistent effect on the synthesis in normal subjects. Administration of cholestyramine resulted in a marked rise in the incorporation of [14C] acetate into sterols, while the administration of chenodeoxycholic acid did not significantly reduce basal sterol synthesis in normal subjects.

These results demonstrate that in man the rate of sterol synthesis in intestinal mucosa is altered in response to physiological variables. Although these findings indicate that sterol synthesis in this tissue is subject to regulation, no difference was observed in basal sterol synthesis between normal subjects and patients heterozygous for familial hypercholesterolaemia.
Exercise‐induced release of pancreatic polypeptide and its inhibition by propranolol: evidence for adrenergic stimulation
Authors: FEURLE G. E. , WIRTH A. , DIEHM C. , LORENZEN M. , SCHLIERF G.
Published: March 2008

Abstract. Pancreatic polypeptide (PP) has been considered to be predominantly under cholinergic‐vagal control and may therefore serve as an indicator of vagal tone. We found similar basal plasma concentrations of PP in athletes with bradycardia and in untrained subjects. We further observed that physical exercise‐an adrenergic situation‐induces a several‐fold rise in PP plasma concentration. Maximal plasma PP levels correlated positively with maximal blood pressure. The exercise‐induced rise of PP was completely abolished by propranolol. These findings suggest that stimulation of the adrenergic system releases PP and that therefore plasma PP concentrations cannot be used to determine cholinergic‐vagal activity.
Prevention of early postmenopausal bone loss: controlled 2‐year study in 315 normal females
Authors: CHRISTIANSEN CLAUS , CHRISTENSEN MERETE S. , McNAIR PETER , HAGEN CLAUS , STOCKLUND KNUD‐ERIK , TRANSBØL IB
Published: March 2008

Abstract. With the aim of preventing postmenopausal bone loss, a placebo‐controlled double‐blind trial of 2 years duration was performed. We randomized 315 healthy volunteers in their early natural menopause to seven treatment and three placebo groups: 17β‐oestra‐diol, oestriol and sequential norethisteron (hormones); bendroflumethiazide 5 mg/day (thiazide); hormones and thiazide; sodium fluoride 20 mg/day; vitamin D3 2000 IU/day (D3); fluoride and D3; and lα (OH) vitamin D3 0–25 μg/day (lαD3). All participants were given daily calcium supplement of 500 mg. Every 3 months we measured the bone mineral content (BMC) of both forearms by photon absorptiometry and chemical quantities in blood and 48 h urinary collections. The study was completed by 264 (84%).

The combined placebo groups snowed a linear fall in BMC reaching 3‐3 % after 2 years (P < 0–001). Hormones and hormones and thiazide led to a 2–5% gain in BMC (P < 001). Thiazide alone postponed the BMC fall for 6 months. After 2 years the thiazide group showed a BMC fall of 1–5% (P < 0–05), less than that of the placebo group (P < 0–05). BMC declined by 3–6%, 4–5%, 3–7% and 3–7% during the respective use of fluoride, D3, fluoride and D3 and lαD3. Nevertheless, the urinary calcium excretion during lαD3 and D3 treatment was 1‐1‐5 mmol/day higher than in the placebo groups.

Apparently, there is no real alternative to oestro‐gen/gestagen in the prevention of postmenopausal osteoporosis.
The effect of maximal exertion on the levels of plasma peptides in cyclists with different physical working capacities
Authors: MARKIEWICZ K. ONSTANTY , LUTZ WALDEMAR , CHOLEWA MARIAN
Published: March 2008

Abstract. The studies were carried out on thirty‐one sportsmen, cyclists aged 21–28 years, after the termination of a training course just before the start of their season. They exercised on a bicycle ergometer according to the following schedule: 30 N at 60 rev/min for 6 min, 40 N at 70 rev/min for 5 min, 50 N at 80 rev/min for 5 min and 50 N at 90 rev/min until exhaustion. According to the level of training the subjects were divided into three groups. In the three groups of cyclists were determined the concentrations of total plasma peptides and their individual fractions obtained by gel‐filtration on Sephadex G‐10.

It was found that the total plasma peptide concentration varied with the level of fitness. The lowest plasma peptide concentration was observed in cyclists with the lowest level of fitness and it differed from those observed in cyclists with intermediary and high levels of fitness. After exercise the biggest increase in plasma peptide concentration was found in the cyclists with the low level of fitness, and the lowest one in those with the high level of fitness.

Individual plasma peptide fractions also revealed differences before and after exercise depending on the level of fitness.
Bile acids and their sulphated and glucuronidated derivatives in bile, plasma, and urine of children with intrahepatic cholestasis: effects of phenobarbital treatment
Authors: STIEHL A. , BECKER M. , CZYGAN P. , FROHLING W. , KOMMERELL B. , ROTTHAUWE H. W. , SENN M.
Published: March 2008

Abstract. Bile acids and their sulphated and glucuronidated derivatives were studied in three children with persistent intrahepatic cholestasis, two children with intrahepatic biliary hypoplasia, and four healthy children.

In children with cholestasis, biliary bile acids consisted of 11(±0–3) % 3 β‐hydroxy‐delta‐5‐cholenoic acid, 2‐1(± 0–6) % lithocholic acid, 2‐2(± 11) % deoxy‐cholic acid, 5–8(±2‐2) % ursodeoxycholic acid, 39‐1(± 1 ‐4) % chenodeoxycholic acid, 0–5(± 0 2) % hyo‐cholic acid, and 49‐3(± 3 0) % cholic acid. Of these bile acids 121 (±l 9) % were sulphated and 4–5 (±0 6) % were glucuronidated. In healthy children, biliary bile acids consisted of 0–7 (±0–4) % lithocholic acid, 3–4 (±0 8.) % deoxycholic acid, 0–1 (±0 1) % ursodeoxycholic acid, 32‐7 (±6 9) % chenodeoxycholic acid, and 631 (±7 1) % cholic acid. Of these bile acids, 0–6±0 1 % were sulphated and 0–2 ±0 1% were glucuronidated (mean ± SEM).

In the urine of healthy children, 3‐3(±0 6) mg/24 h bile acids (1–5±0 3 mg sulphates and 0–1 ±0 1 mg glucuronides) were excreted, in the urine of children with cholestasis 61‐4 (± 10 2) mg/24 h (30 2 ±7 1 mg sulphates and 5 6 ±1 2 mg glucuronides) were excreted. Thus in children with cholestasis the amounts of sulphated and glucuronidated bile acids are greater than in healthy controls. Substantial amounts of sulphated and glucuronidated bile acids are excreted in bile and urine of these patients.

Phenobarbitone treatment in the five children with cholestasis led to a reduction of serum bile acids from 90 4 (± 13 2) μg/ml to 39 3(±3 6) μ//ml, a relative increase of bile acid glucuronides in bile from 45 (±0 6)% to 8 l(±0 6)%, a slight alteration of the bile acid sulphates in bile from 121(±l 9) % to 111 (± 1 2)% and no alteration of the bile acid spectrum. Urinary excretion of bile acids decreased from 61 4 (± 10 2) mg/24 h to 34 7(±3 0) mg/24 h. Phenobarbitone treatment of children with cholestasis thus induced glucuronidation of bile acids but had no significant effect on sulphation or on formation of individual bile acids.
Parathyroid hormone fragments in secretory granules of human parathyroid adenomata
Authors: MOHR HARALD , HESCH ROLF‐D. , McINTOSH CHRISTOPHER H. S. , JOPPNER HARALD
Published: March 2008

Abstract. The composition of human parathyroid hormone immunoreactivity in the secretory granule fraction of parathyroid hormone adenomata was investigated. Granular extracts were separated by gel filtration and the eluates assayed by radioimmunoassay and sequence specific immunoradiometric assays detecting aminoterminal and carboxyterminal activity. About half of the extracted adenomata contained fragments besides intact hormone. The fragment composition varied from adenoma to adenoma.
Inhibition of human fat cell adenylate cyclase mediated via alpha‐adrenoceptors
Authors: KATHER HORST , PRIES JOCHEN , SCHRADER VOLKER , SIMON BERND
Published: March 2008

Abstract. Human adipose tissue contains alpha‐ as well as β‐adrenoceptor sites mediating antagonistic catecholamine effects on lipolysis. To characterize the mechanisms of catecholamine action in biochemical terms we have studied the effects of the almost pure β‐adrenoceptor agonist isoproterenol and of the mixed adrenergic agonist adrenaline on human fat cell adenylate cyclase in the presence of alpha‐ and β‐adrenoceptor blocking drugs.

In contrast to the almost pure β‐adrenergic agent isoproterenol, the mixed agonist adrenaline, besides its stimulatory action, also had inhibitory effects which became apparent upon complete β‐adrenoceptor blockade using 005 mmol/1 propranolol. Under these conditions adrenaline caused a dose‐dependent inhibition of basal and parathyroid hormone‐activated enzymic activity with a maximum of 30–50%, which was dependent on GTP and could be reversed by simultaneous alpha‐adrenergic blockade using 5 μmol/1 dihydroergotamine or 10 μmol/1 phentolamine. These results support the concept of antogonistic alpha‐ and β‐adrenoceptor sites coexisting as regulatory subunits of the human fat cell adenylate cyclase.
Bile acid synthesis and excretion following release of total extrahepatic cholestasis by percutaneous transhepatic drainage
Authors: EKLUND ARNE , NORLANDER ANDERS , NORMAN ARNE
Published: March 2008

Abstract. Urinary, biliary and serum bile acids were studied in three patients before and after percutaneous transhepatic drainage for total bile duct obstruction.

Before drainage high urinary excretion often different bile acids occurred. The percentage distribution was: cholic and chenodeoxycholic acid (66–86%), hyo‐cholic (3–16%), 3β 12α‐dihydroxy‐5‐cholenoic (3–6%) and 3β‐hydroxy‐5‐cholenoic acid (2–8%). These acids were regularly found in serum. In addition small amounts (less than 2%) of norcholic, allocholic, 3β, 7α‐dihydroxy‐5β‐cholanoic, 3α, 7α‐dihydroxy‐5α‐cholanoic and lithocholic acid were excreted in urine. Trace amounts of these bile acids were found in serum.

After start of drainage biliary bile acid excretion increased rapidly during the first day, dropped to a minimum during the second or third day and then slowly increased again. In spite of normal volumes of bile produced, the total serum bile acids and the urinary excretion of bile acids remained increased during a drainage period of 19 days. The bile acids were of the same type as observed during cholestasis. In serum the increase was mainly due to high concentrations of chenodeoxycholic and 3β‐hydroxy‐5‐cholenoic acid, as sulphate esters.

Glycine and taurine conjugates of cholic, chenodeoxycholic and hyocholic acid were mainly excreted in bile. Bile acid sulphate esters were only present in trace amounts in bile and were mainly excreted in urine. This, combined with low renal clearance, explains the elevated serum levels of sulphate esters of chenodeoxycholic and 3β‐hydroxy‐5‐cholenoic acid conjugates.