bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of the monooxygenase enzyme system in human lung
Authors: OHNHAUS E. E. , BLUHM R. C.
Published: March 2008

Abstract. In the present study, lung tissue of patients suffering from tuberculosis and undergoing thoracic surgery was investigated. All these patients were treated prior to surgery by an anti‐tuberculous drug regimen, including rifampicin, for 3–6 months. Patients having non‐malignant lung disease served as controls. In the lung tissue obtained, 7‐ethoxycou‐marin‐0‐deethylase as a substrate of monooxygenase activity, epoxide hydrolase and glutathione‐S‐transferase were measured. Monooxygenase activity increased from 0·62 + 0·10 pmol mg protein‐1 min‐1 in the control group to 1·55 ± 0·34 pmol mg protein‐1 min‐1 (P<0·02) following anti‐tuberculous drug treatment, while the other enzymes remained unchanged. Rifampicin, a potent inducer of hepatic metabolism in man, seems a likely cause for the changes in monooxygenase activity, since for other anti‐tuberculous drugs no enzyme‐inducing effect has so far been reported in any tissue in man. In addition, the activity of the disease seems to be of great importance for the extent of induction. Thus, in patients with active tuberculosis, higher monooxygenase activities were found, compared to those with inactive disease (1·92 ± 0·53 vs. 0·99 ± 0·24 pmol mg protein‐1 min‐1), both showing even higher values than controls.
Changes in energy expenditure and fat metabolism in rats infused with interleukin‐1
Authors: TOCCO‐BRADLEY ROSALIE , GEORGIEFF M. , JONES CATHERINE T. , MOLDAWER L. L. , DINARELLO C. A. , BLACKBURN G. L. , BISTRIAN B. R.
Published: March 2008

Abstract. Metabolic alterations related to resting energy expenditure (REE) and fat metabolism have been noted during sepsis, and often depend on the causative agent and the stage and severity of the illness. We studied the effect of IL‐1, the protein mediator of the ‘acute phase’ response during infection, on REE, respiratory quotient (RQ), and fat metabolism in male rats (210 g), who were infused over an 8‐h period with (1 ‐14C)‐palmitate (PALM), (2‐3H)‐glycerol (GLY) and either saline or interleukin‐1 (IL‐1). At 7–8 h post infusion, the IL‐1 group showed a significant increase in REE but no change in RQ. The IL‐1 group also exhibited a significant decrease in strum free fatty acid (FFA) and an increase in FFA clearance. Free fatty acid flux, %PALM oxidation, serum (GLY), glycerol clearance, and glycerol flux (a measure of lipolytic rate) were not significantly different between the two groups. We conclude that IL‐1 can mimic the increase in REE seen during infection; the increase in REE is not due to a selective increase in fat oxidation only, although the unchanged RQ and increased REE suggest that there is a proportional increase in net FFA oxidation.
Monoclonal anti‐HBs antibodies radioimmunoassay and serum HBV‐DNA hybridization as diagnostic tools of HBV infection: relative prevalence among HBsAgnegative alcoholics, patients with chronic hepatitis or hepatocellular carcinomas and blood donors
Authors: POL S. , THIERS V. , NALPAS B. , DEGOS F. , GAZENGEL C. , CARNOT F. , TIOLLAIS P. , WANDS J. R. , BERTHELOT P. , BRECHOT C.
Published: March 2008

Abstract. Anti‐HBs monoclonal antibodies radioimmunoassay (m‐RIA) and HBV‐DNA hybridization techniques were used to detect HBs antigen (HBsAg)—associated determinants (evidence of HBV on‐going infection) and HBV‐DNA sequences (evidence of viral multiplication) in the serum samples of 479 patients who were HBsAg negative by standard solid‐phase radioimmunoassay. They included 128 alcoholics, 104 patients with chronic hepatitis, fifty‐four with an hepatocellular carcinoma, 100 with coagulation disorders and ninety‐three blood donors. The aim of this study was the comparison in these populations of the prevalence of the various HBV markers. m‐RIA detected HBsAg‐associated determinants in 1% of blood donors, 3% of coagulation disorders, 3·1% of the alcoholics, 21·1% of chronic hepatitis and 16·6% of hepatocellular carcinoma; hybridization identified HBV‐DNA sequences in 0·9%, 2·2%, 10·9%, 9·6% and 5·5% of these cases, respectively. The combined prevalence of both markers of an on‐going HBV infection (with or without viral multiplication) was 14·16%, 26·9% and 22·2% in the latter groups, respectively, as compared with only 3% in patients with coagulation disorders and 2·1% of blood donors. These results confirm the frequency of HBV or HBV‐related virus infection in alcoholics, in chronic hepatitis and hepatocellular carcinomas, despite the absence of HBsAg by standard RIA (or even of any other usual marker); this gives further evidence for variations in the expression of HBV infection. A high and quite similar prevalence of usual serum markers and hybridization results was observed in the alcoholics and in the patients with chronic hepatitis. By contrast, in the former there was an about seven‐fold lower positivity of m‐RIA, in which alcohol consumption could play a role by impairing HBsAg secretion.
Human platelet factor 4 and protamine sulphate interaction with glycosaminoglycans in the rabbit
Authors: CELLA G. , MYERS C. J. , PROSDOCIMI M. , SASAHARA A. A.
Published: March 2008

Abstract. We studied the action of protamine sulphate on human platelet factor 4 (PF4) kinetics in rabbits in the presence of various glycosaminoglycans (CAGs). The animals pretreated with heparin showed high initial PF4 levels with a subsequent slow monoexponential clearance. The PF4 kinetics, in the presence of heparan and dermatan sulphate, reflected the different affinities that PF4 has for these GAGs. Protamine, at dosages that totally neutralized 1000 USP units of heparin pretreatment, caused an immediate disappearance in the circulating PF4. However, a second heparin injection 10 min after protamine, induced a PF4 peak release. It is possible that protamine displaced the PF4 from the binding sites of heparin, releasing it for storage in the body ‘pool’, from where it can be harvested again. The action of protamine on PF4 kinetics in the rabbits pretreated with 30 mg heparan sulphate was similar to that obtained with heparin pretreatment; however, a higher dose of protamine was required to obtain the optimal effect. After a 20 mg dose of protamine, unexpectedly, a bolus of heparin did not produce any peak release of PF4 in the rabbits pretreated with 30 mg of dermatan sulphate. Although part of the protamine will displace PF4 from the binding sites of the dermatan sulphate molecule, the remaining part of protamine could probably be bound to this GAG without losing its activity so that, upon subsequent heparin injection, it is immediately neutralized, rendering it unavailable for further PF4 harvesting.
Effects of Trimoprostil, a prostaglandin E2 analogue, on human gastric acid secretion and soluble mucin output
Authors: LEE S. P. , NICHOLLS JANE F. , ROBERTSON A. M.
Published: March 2008

Abstract. We have studied the effects of Trimoprostil, a prostaglandin E2 analogue, on gastric acid and soluble mucus output using human subjects. This compound caused anti‐secretory effects on both basal as well as histamine‐stimulated gastric acid secretion in a dosedependent manner. There was a simultaneous increase in total mucus output. When the secreted mucus was fractionated by Sepharose CL‐2B gel chromatography, most of the basal gastric mucin was shown to be in the polymeric form (mol wt 2 times 106), whereas after histamine stimulation the mucin was mostly in the subunit form (mol wt 0·5 times 106). The gastric mucin, after stimulation using low doses of prostaglandin, was mainly in the polymeric form; but after higher doses, the subunit form predominated. These observations are important in the understanding of physiological and pharmacological control of gastric mucus output with regard to its chemical composition and molecular heterogeneity, and provide further insight into the rational clinical use of the prostaglandins for gastroduodenal diseases.
Increased levels of platelet‐activating factor in blood from patients with cirrhosis of the liver
Authors: CARAMELO C. , FERNÁNDEZ‐GALLARDO S. , SANTOS J. C. , IÑARREA P. , SÁNCHEZ‐CRESPO M. , LÓPEZ‐NOVOA J. M. , HERNANDO L.
Published: March 2008

Abstract. The levels of platelet‐activating factor (pafacether) were measured in blood and ascitic fluid from cirrhotic patients and in blood from a group of controls, using a recently described technique for extraction and measurement. In addition, activity of acetylhydrolase, the main catabolic enzyme for paf‐acether, was also measured. The highest levels of paf‐acether in blood were found in decompensated cirrhotics (1·78 pL 0·62 ng ml‐1; mean pL SD, n= 8). Compensated cirrhotics showed lower blood values (0·79 pL 0·21, n= 4), but higher than controls (0·20 pL 0·04, n= 12). Paf‐acether levels in ascitic fluid were similar to those of blood. Values of acetylhydrolase in serum were similar in all the groups studied (3·0 pL 0·4 in cirrhotics vs. 2·3 pL 0·4 nmol min‐1 mg‐1 of protein in controls). These data suggest an enhanced production of paf‐acether in cirrhotic patients rather than a decreased catabolism. High levels of paf‐acether in blood could be involved in the impaired haemodynamics of cirrhotic patients and in their renal function alterations.
Very low density lipoprotein metabolism after insulin over‐treatment and during a euglycaemic clamp
Authors: KRUSZYNSKA Y. T. , HOME P. D. , ALBERTI K. G. M. M.
Published: March 2008

Abstract. The disturbance of very low density lipoprotein (VLDL) metabolism that occurs as a result of intensive insulin treatment and during a euglycaemic clamp have been investigated in a rat model. Normal rats were maintained with fed blood glucose levels below 5 mmol l‐1 for 8 weeks by subcutaneous insulin injections (normal fed levels 5·8 pL 0·4 (SD) mmol l‐1). Glucose requirement to maintain a glucose clamp was significantly reduced (116 pL 3 μmol min‐1 kg‐1 (SE) vs. 173 pL 5 μmol min‐1 kg‐1, P < 0·001), compared with weight‐matched normal control rats. In the fasting state (blood glucose 3·5 pL 0·2 mmol l‐1 vs. 3·9 pL 0·1 mmol l‐1, NS) plasma non‐esterified fatty acid levels were reduced. Fasting VLDL‐triglyceride turnover, measured by bolus injection of 14C‐VLDL, was also lower (3·17 pL 0·12 μmol min‐1 kg‐1 vs. 3·50 pL 0·07 μmol min‐1 kg‐1, P < 0·05). Despite decreased turnover, insulin over‐treated rats had normal plasma triglyceride concentrations indicating a removal defect. At the end of a 3‐h euglycaemic clamp, plasma triglyceride concentrations and VLDL‐triglyceride turnover were decreased in both normal control and insulin over‐treated animals, and turnover remained significantly lower in the insulin over‐treated rats (2·59 pL 0·13 μmol min‐1 kg‐1 vs. 3·08 pL 0·10 μmol min‐1 kg‐1, P < 0·05). Triglyceride metabolic clearance rate remained abnormally low in the insulin overtreated animals (4·06 pL 0·10 ml min‐1 kg‐1 vs. 5·91 pL 0·17 ml min‐1 kg‐1, P < 0·001). This was associated with a significant decrease in skeletal muscle lipoprotein lipase activity in both the fasting state and at the end of the clamp. Adipose tissue lipoprotein lipase activity was not different between the two groups under these conditions, and did not change with the clamp. In ad libitum fed rats adipose tissue lipoprotein lipase activities were much higher than during the clamps, particularly in the insulin overtreated animals (47·4 pL 1·5 vs. controls 28·5 pL 1·7 U g‐1 wet wt, P < 0·001). The findings indicate that long term over‐insulinization is associated with insulin insensitivity, decreased quadriceps muscle lipoprotein lipase activity, and decreased plasma VLDL‐trigylceride clearance.
A new model to assess deoxycholic acid metabolism in health using stable isotope dilution technique
Authors: STELLAARD F. , PAUMGARTNER G.
Published: March 2008

Abstract. A model has been developed that permits calculation of the absorption rates of newly formed and deconjugated deoxycholic acid (DCA) from the intestine, the fractional absorption rate of deconjugated DCA and the daily rate of formation of DCA. The model is based on steady state conditions and isotopic equalities of conjugated DCA in blood and in the enterohepatic circulation, as well as between unconjugated DCA in blood and in the intestinal content. The model requires measurement of isotopic enrichment in the conjugated and unconjugated fractions of DCA in serum after administration of an isotopic label. The measurements were carried out in seven healthy volunteers using capillary gas chromatography/mass spectrometry after oral administration of 24‐13 C‐DCA. Intestinal absorption of deconjugated DCA exceeded that of newly formed DCA: (mean pL SD) 7·4 pL 5·6 vs. 4·5 pL 2·1 μmol kg‐1 d‐1. Total absorption of unconjugated DCA (11·9 pL 6·9 μmol kg‐1 d‐1) accounted for approximately 6% of estimated total intestinal DCA absorption. The fractional absorption rate of unconjugated DCA in the intestine averaged 55·5 pL 15·1%; 8·2 pL 3·3 μmol kg‐1 d‐1 DCA were formed daily by 7α‐dehydroxylation of cholic acid. This rate of DCA formation compares well with values for foecal DCA excretion (15 μmol kg‐1 d‐1) and cholic acid synthesis rate (11·9 μmol kg‐1 d‐1) obtained in comparable controls by the same laboratory. Also good agreement is obtained with data calculated for 7α‐dehydroxylation of cholic acid in the fasting state by Hofmann et al. (J. Clin. Invest. 1983;71:1003–22) using a simulated physiological pharmacokinetic computer model (5 μmol kg‐1 d‐1).
Messenger RNA content and complexity in normal and overloaded rat heart
Authors: BASTIE D. DE LA , MOALIC J. M. , BERCOVICI J. , BOUVERET P. , SCHWARTZ K. , SWYNGHEDAUW B.
Published: March 2008

Abstract. Cardiac overload was studied in rats by abdominal aortic constriction, which increased the left ventricular weight by 59% after 12 days. During the transition, which precedes the compensatory hypertrophy, both total RNA and poly(A)‐containing messenger RNA increased. The concentration of these polynucleotides peaked by day 4 after constriction, rising from 1·27 pL 0·3 to 1·88 pL 0·2 mg g‐1 fresh weight for total RNA, and from 38 pL 24 to 62 pL 12 μg g‐1 fresh weight for poly(A)‐containing RNA, and returned to normal by day 12. However, the total amount per ventricle of both RNAs remained high. Poly(A)‐containing RNA prepared from normal heart was hybridized to its cDNA copy. These results were expressed as the percentage of hybridization vs. the log 10 of the product of the poly(A)‐containing RNA concentration and the time (Rot), and in computer analysis were described by division into three different frequency components. In normal hearts, the Rot 1/2 values of these components were, respectively, 3·98 times 10‐3, 0·338 and 21·380 mol.s.l‐1, which correspond to 2–3, 240 and 12 200 different sequences that were copied 22 000–33 000, 310 and 5 times, respectively. Four and 30 days after banding there was a harmonious enhancement of the number of the copies without any change in the number of different sequences, and the three different hybridization curves were superimposed. In conclusion, cardiac overload raises the poly(A)‐containing RNA concentration, probably by stimulating transcription, but no major changes occur in any of the frequency classes.
Responses of peripheral blood cells and lymphocyte subpopulations to insulin‐induced hypoglycaemia in human insulin‐dependent (Type 1) diabetes
Authors: FISHER B. M. , SMITH J. G. , McCRUDEN D. C. , FRIER B. M.
Published: March 2008

Abstract. Changes in counts of peripheral blood cells including lymphocytes and lymphocyte subpopulations were examined in response to acute insulin‐induced hypoglycaemia in fourteen insulin‐dependent diabetic patients of differing duration, and in eight normal subjects. In patients with a short duration of diabetes (less than 5 years) an initial lymphocytosis preceded a later granulocytosis, similar to changes in the normal group following hypoglycaemia. The lymphocytosis comprised increments in T11 (total), T4 (helper), and T8 (suppressor/cytotoxic) lymphocyte subsets, but B lymphocytes did not rise. In diabetic patients of longer duration (greater than 15 years) the initial lymphocytosis was attenuated, the T4 subset response being absent and the T11 subset response was diminished. The lower lymphocyte responses in the long‐term diabetics were unrelated to differences in the hormonal responses to hypoglycaemia or to the rate of blood glucose recovery. Rapid mobilization of specific lymphocyte subpopulations appears to be abnormal in long‐term insulin‐dependent diabetes, and may indicate underlying immunological dysfunction.
Dihydralazine induces marked cerebral vasodilation in man
Authors: SCHROEDER T. , SILLESEN H.
Published: March 2008

Abstract. Dihydralazine is widely used for acute control of hypertension. In experimental studies it seems to dilate cerebral resistance vessels and increase intracranial pressure. However, the effect on cerebral blood flow (CBF) in man has been little studied. Measurements of CBF were performed with the i.v. xenon‐133 technique in seven young, normotensive volunteers before and 15, 60 and 180 min after 6·25 mg i.v. dihydralazine, corresponding approximately to 0·1 mg kg‐1 body weight. For comparison the CBF reactivity to inhalation of 5% CO2 in air was investigated. Dihydralazine increased CBF throughout the period of study, in median 16, 27 and 23% at the three periods of measurements, respectively. The arterial blood pressure remained unchanged, whereas heart rate increased significantly. During CO2 inhalation, CBF increased on average 29%. Thus, the cerebral vasodilation exerted by a small i.v. dose of dihydralazine was of the same order of magnitude as the effect of 5% CO2 inhalation. These results in normal subjects should be extrapolated to diseased persons only with extreme caution. Still, the very marked and long lasting vasodilation observed suggests that dihydralazine, from a theoretical point of view, in certain clinical situations may be harmful.
Studies on collagen metabolism in the Marfan syndrome
Authors: MÜLLER K. P. , NERLICH A. G. , KUNZE D. , MÜLLER P. K.
Published: March 2008

Abstract. The pattern of collagen metabolism was studied in nine fibroblast cultures from Marfan patients. The cellular synthesis of collagen and non‐collageneous proteins was significantly increased, whereas secretion and degradation remained unchanged. Other steps of post‐translational processing such as hydroxylation of prolyl or lysyl residues, affecting triple helix stability, were found to be normal. Furthermore, peptide mapping of isolated a 1(I), a2(I) and al(III) gave no evidence for structural defects. Hence, our study would support the notion that defects other than those affecting collagen type I or III metabolism must represent the molecular basis of the Marfan syndrome.
Bactericidal capacity against Neisseria meningitidis of normal human serum and sera with functional deficiencies of the third and eighth complement factor
Authors: STRATE M. , OLSEN H. , TEISNER B.
Published: March 2008

Abstract. The bactericidal capacity of serum with C3 deficiency secondary to circulating C3 nephritic factor, serum with C8 deficiency and normal human serum were assessed in vitro against Neisseria meningitidis groups A‐C. Normal human serum and C8‐deficient serum, originating from a 28‐year‐old male with two episodes of meningococcal meningitis, showed significant bactericidal capacity against meningococci groups A and B. Against group C meningococci the C8‐deficient serum revealed significant bactericidal capacity, whereas normal human serum showed no bactericidal effect. Serum with C3 deficiency, obtained from a 16‐year‐old female with two episodes of meningococaemia, showed no bactericial effect against meningococci groups A–C. Incubation of normal human serum and C8‐deficient serum with isolated nephritic factor resulted in C3 depletion and abolished the bactericidal effect.
Normal pathways for glucuronidation, sulphation and oxidation of paracetamol in Gilbert's syndrome
Authors: ULLRICH D. , SIEG A. , BLUME R. , BOCK K. W. , SCHRÖTER W. , BIRCHER J.
Published: March 2008

Abstract. A group of eleven subjects with Gilbert's syndrome was characterized by conventional tests and determination of bilirubin and its conjugates in plasma by alkaline methanolysis and thin layer chromatography. After a 1 g dose of paracetamol h.s. the drug and its metabolites were measured by high performance liquid chromatography (HPLC) in the overnight 8‐h urine sample. The amounts of paracetamol and of its metabolites recovered in urine were almost identical with those found in the control group (n= 10). The glucuronide: paracetamol ratio, which is considered to be an index of glucuronidation, was not correlated with the fraction of bilirubin present in plasma as glucuronides. These data do not suggest that in subjects with Gilbert's syndrome therapeutic doses of paracetamol are associated with an increased risk for hepatic or systemic toxicity.
Priming of neutrophils for enhanced oxidative burst by sputum from cystic fibrosis patients with Pseudomonas aeruginosa infection
Authors: KHARAZMI A. , RECHNITZER C. , SCHIØTZ P. O. , JENSEN T. , BAEK L. , HØIBY N.
Published: March 2008

Abstract. Neutrophils accumulate in the lungs of cystic fibrosis (CF) patients and inflict tissue damage by release of oxygen radicals and proteases. Here we report on the ability of sputum to prime neutrophils for enhanced release of oxygen radicals. Sol phase was prepared by ultracentrifugation of sputum obtained from CF patients attending the CF Clinic, Rigshospitalet, Copenhagen. The oxidative burst response of neutrophils from healthy individuals was measured by oxygen consumption, superoxide production and chemiluminescence. Neutrophils were preincubated with sputum or buffer and then stimulated with f‐Met‐Leu‐Phe or zymosan. Appropriate controls were included in the experiments. It was shown that neutrophils preincubated with CF sol phase and stimulated with f‐Met‐Leu‐Phe generated a three‐ to five‐fold higher chemiluminescence response than those preincubated with buffer. There was no enhancement of the response when zymosan was used for stimulation of the cells. Neutrophils incubated with sol phase alone exhibited no response. Attempts were made to identify and partially characterize the priming factor(s). It was found that the sputum samples contained bacterial endotoxins. The priming activity was resistant to heating at 100°C for 15 min, and was present only in fractions with molecules larger than 100 KD. It is suggested that the priming factor(s) consist of bacterial endotoxins and/or immune complexes. Activation and enhanced release of oxygen radicals from neutrophils may play an important role in the host defence as well as pathogenesis of tissue damage in the lungs of these patients.
Highly significant negative correlations between erythrocyte aggregation value and serum concentration of high density lipoprotein cholesterol in a sample from a normal population and in patients with coronary heart disease
Authors: RUHENSTROTH‐BAUER G. , MÖSSMER G. , OTTL J. , KOENIG‐ERICH S. , HEINEMANN G.
Published: March 2008

Abstract. In a previous clinical study it was found that patients with coronary heart disease and diabetics with peripheral artery disease often have an elevated erythrocyte aggregation value (AW) and that there is a positive correlation between AW and the number of risk factors found in a subject. In the present investigation we studied the relationship between AW and the serum concentration of high density lipoprotein cholesterol (HDL‐C), which is known to be inversely associated with coronary heart disease (CHD) incidence. We found highly significant negative correlations between AW and HDL‐C both in a subsample of the study population of a cross‐sectional epidemiologic study on CHD risk factors (First Survey of the MONICA Project Augsburg) and in male patients with angiographically confirmed CHD. Correlation coefficients were –0·233 for normal men (P < 0·01, n= 136), –0·261 for normal women (P < 0·01, n= 117), and –0·745 for CHD patients (P < 0·01, n= 14). The results support the concept that the erythrocyte aggregation value as an indicator of cardiovascular risk is consistent with established risk factor associations.
A light microscopic and biochemical study of carbon tetrachloride‐induced pulmonary fibrosis in rats: the preventive effect of malotilate
Authors: PÄÄKKÖ P. , ALA‐KOKKO L. , RYHÄNEN L.
Published: March 2008

Abstract. Orally administered malotilate was studied as a protective anti‐fibrotic agent with respect to experimentally induced pulmonary fibrosis in rats. Intraperitoneally‐injected carbon tetrachloride (CCl4) significantly increased the lung weight to body weight ratio, lung total protein and total hydroxyproline content, while the relative protein content of the lungs decreased. CCl4 induction caused diffuse alveolar damage and inflammatory changes mimicking usual interstitial pneumonia with interstitial fibrosis. The morphological findings suggest a primary toxic effect on the lungs. Treatment with malotilate completely normalized the lung weight to body weight ratio, lung total and relative protein content and total hydroxyproline content. Morphologically, malotilate seemed to prevent the exudative inflammatory changes and interstitial fibrosis, but not the primary toxic effect of CCl4 on the capillary endothelium or the alveolar epithelium, the result of which was diffuse alveolar damage. It is concluded that malotilate may be a useful drug for the prevention of pulmonary fibrosis.
Relationship between growth hormone and Somatomedin‐C levels in untreated acromegaly, after surgery and radiotherapy and during medical therapy with Sandostatin (SMS 201–995)
Authors: LAMBERTS S. W. J. , UITTERLINDEN P. , VERLEUN T.
Published: March 2008

Abstract. Several conflicting reports have been published with regard to the relationships between circulating growth hormone (GH), Somatomedin‐C (SM‐C) levels and clinical activity during different stages of therapy of acromegaly. We did not find a significant correlation between (fasting, post‐prandial and mean 24‐h) plasma GH and SM‐C concentrations in twenty‐two untreated acromegalic patients. There was a statistical significant correlation, however, if only the GH levels below 100 μg l‐1 were considered (n=18 patients, P<0·01). The distribution of molecular forms of GH (‘little’, ‘big’ and ‘big‐big’) did not differ between the four patients with GH levels above 100 μg l‐1 and in four patients with levels between 40 μg l‐1 and 80 μg l‐1. Therefore, it is suggested that GH levels of 80–100 μg l‐1 maximally activate Somatomedin‐C production in man and that further increases in GH in general will not result in a further increase in SM‐C generation. There was a significant correlation between GH and SM‐C levels in forty‐nine acromegalic patients after surgery and/or radiotherapy (P<0·001). In twenty‐three of thirty‐one patients with elevated SM‐C levels the disease was subjectively still active, while this was the case in none of the patients with normal SM‐C levels. In eight patients the disease was considered not to be clinically active any more, despite slightly increased SM‐C levels. During long‐term therapy of ten acromegalic patients for 16–108 weeks (mean 66±10) with 200–300 μg Sandostatin subcutaneously, clinical activity of the disease disappeared well before mean 24–h GH and SM‐C levels reached the normal levels. There was a close correlation between mean 24‐h GH and SM‐C levels during Sandostatin therapy (P<0·001). ‘Clinical cure’ during this medical treatment was reached in five patients, as reflected by disappearance of subjective complaints, normalization of SM‐C levels and 24‐h mean GH levels of 2·8±0·2 μg l‐1.

Conclusions: (i) in untreated acromegaly, circulating GH and SM‐C levels correlate well up to GH concentrations of 100 μg l‐1. A further increase in GH does not result in a corresponding further increase in SM‐C levels, suggesting a maximally activated production, without further GH‐dependent capacity. (ii) Clinical ‘cure’ of acromegaly often occurs before normalization of the circulating SM‐C levels. (iii) The measurement of plasma SM‐C concentrations can be used well to adjust the dose and frequency of Sandostatin administration in acromegaly. This avoids the need of measuring extensive 24‐h GH profiles.
Collagen type IV and procollagen type III during granulation tissue formation: a serological, biochemical, immunohistochemical and morphometrical study on the viscose cellulose sponge rat model
Authors: HØRSLEV‐PETERSEN K. , PEDERSEN L. R. , BENTSEN K. D. , BROCKS D. , GARBARSCH C. , KIM K. Y. , HAHN E. G. , SCHUPPAN D. , LORENZEN I.
Published: March 2008

Abstract The serum concentrations of collagen type IV,7S, collagen type IV, ncl, and aminoterminal type III procollagen peptide immunoreactive components were measured by means of specific radioimmunoas‐says during development of granulation tissue in rats. The results were compared with tissue deposition of basement membranes and interstitial collagens in the granulation as measured morphometrically. A parallel sequential pattern in tissue deposition of collagen types III and IV, and serum increase of collagen types III‐ and IV‐related fragments, was observed. Serum collagen type IV was less sensitive as a marker for development of granulation tissue than the serum procollagen type III N‐peptide. This was in accordance with a low collagen type IV/interstitial collagen ratio in the granulation tissue. However, a crosssectional study showed that serum collagens types IV,7S and IV.ncl may be useful as early quantitative indicators of granulation tissue formation. Simultaneously, measurement of collagen type IV‐ and procollagen type III N‐peptide‐related antigens in serum provides a differentiated reflection of the dynamic matrix processes in developing granulation tissue.
Action of somatostatin analogue (SMS 201–995) on the growth‐promoting effect resulting from sustained achlorhydria in rat gastric mucosa, with special reference to endocrine cell behaviour
Authors: CADIOT G. , LEHY THERESE , BONFILS S.
Published: March 2008

Abstract We investigated whether a new long‐acting somatostatin analogue (SMS 201–995) could antagonize the trophic effect induced by hypergastrinaemia, resulting from chronic omeprazole treatment, on the rat gastric mucosa and particularly on endocrine cell growth. SMS was administered concomitantly with omeprazole for 70 days. Gastric morphometric and cell proliferative parameters, gastric acid secretion and plasma gastrin levels were examined. New findings with omeprazole pointed out: (i) a trophic effect on the antral mucosa and (ii) that the increase observed in gastrin cell number was not due to stimulation of gastrin cell production by omeprazole but more likely to a prolongation of the gastrin cells' life span. As compared to omeprazole alone, simultaneous SMS administration significantly decreased the parietal cell (P < 0·05) and gastrin cell (P < 0·01) labelling indices, mucosal height of total glandular stomach (P < 0·05) and antral mucosal height (P < 0·05). It tended to lower fundic mucosal height and fundic argyrophil cell density (P < 0·2 and P < 0·1, respectively). SMS, in our conditions, did not accentuate the inhibitory effect of omeprazole on gastric acid secretion nor reduce high plasma gastrin levels. We conclude that SMS modestly counteracts the growth‐promoting effect observed in rat gastric mucosa after prolonged omeprazole treatment.
Intestinal development in the suckling rat: effect of insulin on the maturation of villus and crypt cell functions
Authors: BUTS J.‐P. , KEYSER NADINE DE , DIVE C.
Published: March 2008

Abstract The influence of insulin on the postnatal development of intestinal functions linked to villus cells (sucrase, lactase, maltase and aminopeptidase) and crypt cells (secretory component of immunoglobulins, SC) has been studied in suckling and weanling rats. At 9 days of age, the animals received a daily injection of insulin 12·5 mU g‐1body weight day‐1for 4 days. Compared with saline‐treated controls, insulin had no effect on the development of the intestinal mucosal mass parameters determined in the jejunum, ileum and colon. A premature appearance of sucrase was noted in isolated jejunal villus and crypt cells, the level of activity reached by the enzyme being dependent of the amount of insulin injected. By 6 and 12 h after a single injection of the hormone (12·5 mU g‐1body weight), sucrase activity was detected in all the cell fractions along the villus‐crypt axis. In villus cells of insulin‐treated rats, maltase, lactase and aminopeptidase activities were significantly (P < 0·001) increased (+201%, +50%, +207%, respectively, vs. controls), whereas the concentration of SC measured by a sensitive immunoradiometric assay was enhanced over the controls by 75% in villus cells, 83% in crypt cells and 172% in the liver. Weanling rats treated from day 10 to day 20 postpartum with 12·5 mU insulin also exhibited a higher intestinal production of SC (+93%, P < 0·01) than did saline controls. The administration of Actinomycin D to 9‐day‐old suckling rats 1 h after insulin injection completely inhibited the adaptative process to the hormone; the activities of sucrase, lactase, maltase and aminopeptidase measured in rats treated with Actinomycin D being equivalent to those recorded in saline controls. Our data demonstrate that: (i) a premature increase of the circulating level of insulin accelerates the maturation of intestinal functions linked to both villus and crypt cells; (ii) the response to the hormone occurs rapidly over the entire villus‐crypt unit, whatever the degree of epithelial cellular differentiation; (iii) the stimulation of the synthesis of brushborder membrane enzymes by insulin appears to be regulated at the level of transcription.
Ethanol decreases plasma sulphydryls in man: effect of disulfiram
Authors: BURGUNDER J.‐M. , NELLES J. , BILZER M. , LAUTERBURG B. H.
Published: March 2008

Abstract Based on animal experiments, interactions of ethanol and its metabolites with sulphydryls have been implicated in the toxicity of ethanol, but acute effects of ethanol on sulphydryls have not been documented in man. Plasma free glutathione and cysteine were therefore measured following the administration of 0·2 g kg‐1ethanol to normal healthy volunteers and chronic alcoholics on disulfiram, where the effects of high concentrations of acetaldehyde can be observed. In both groups, plasma glutathione decreased shortly following ethanol, and a sustained decrease in glutathione was seen in the subjects on disulfiram. In patients on disulfiram, but not the healthy controls, plasma cysteine decreased significantly. The decrease in plasma cysteine was correlated to the rise in acetaldehyde, suggesting that cysteine, but not glutathione, forms an adduct with acetaldehyde in man. We conclude that even moderate doses of ethanol may disturb the sulphydryl homeostasis and could interfere with biologically important processes that depend on sulphydryl groups.
A monoclonal Ro‐antibody and the serum of a Ro‐positive patient with subacute cutaneous lupus erythematosus (SCLE) react with basal layers of human epidermis
Authors: MAYET W. J. , BACHMANN M. , PFEIFER K. , SCHRÖDER H. C. , MÜLLER W. E. G. , GUDAT W. , KORTING G. W. , BÜSCHENFELDE K. H. MEYER ZUM
Published: March 2008

Abstract Skin lesions, especially at areas exposed to sunlight, prove to be a major form of manifestation of diseases related to Ro‐antibodies and neonatal‐, ‘ANA‐negative‐’, and cutaneous types of lupus erythematosus. A monoclonal Ro‐antibody established by our group reacts with a 60 kD polypeptide in extracts from human spleen, whereas in extracts from human epidermis the monoclonal Ro‐antibody and a purified Ro‐antibody from a monospecific serum of a patient with subacute cutaneous lupus erythematosus reacted with a 60 kD and a 48 kD protein. Performing immunofluorescence microscopy on HEp2‐cells both antibodies showed a nuclear speckled staining pattern and a reaction with cytokeratin filaments. On skin biopsies obtained from the patient, predominantly the basal layers of the proliferative stratum germinativum demonstrated a high rate of immunofluorescence; antigen‐expression seems to depend on sunlight exposure. From these data we assume that, especially in subacute cutaneous lupus erythematosus, cross‐reaction of the Ro‐antibody with one of the lower molecular keratins happens in that area of human epidermis which histologically shows cellular destruction.
Comparison of the effects of two different doses of alcohol on serum lipoproteins, HDL‐subfractions and apolipoproteins A‐I and A‐II: a controlled study
Authors: VÄLIMÄKI M. , TASKINEN MARJA‐RIITTA , YLIKAHRI R. , ROINE R. , KUUSI T. , NIKKILÄ E. A.
Published: March 2008

Abstract Our earlier studies have shown that heavy alcohol intake increases the serum concentration of HDL2. The present study aimed to test which HDL subfraction is affected by moderate alcohol intake, and to examine the time‐ and dose‐dependency of alcohol‐induced changes in serum lipoproteins. Therefore, 30 or 60 g day‐1 of alcohol were given to 10 healthy male volunteers during two 3‐week periods separated by an abstinence period of 3 weeks. Lipoproteins were fractioned by sequential flotation. On both doses the total HDL3 concentrations rose progressively, the maximum increases being 10 and 25% at the end of respective drinking periods. In contrast, the HDL2 increased slightly only on the dose of 60 g day‐1. The serum concentrations of apoprotein A‐I and A‐II increased on both doses but significantly only on the dose of 60 g day‐1; the increments being 22 and 35%, respectively. On the basis of these and our earlier findings we conclude that (i) the effects of heavy and moderate alcohol intake on serum HDL‐subfractions are different: the former preferentially increases the HDL2 whereas the latter augments the HDL3; (ii) alcohol‐induced changes in serum lipoproteins are both time‐ and dose‐dependent.
Platelet α2‐ and leucocyte β2‐adrenoceptors in phaeochromocytoma: effect of tumour removal
Authors: VALET P. , DAMASE‐MICHEL C. , CHAMONTIN B. , DURAND D. , CHOLLET F. , MONTASTRUC J. L.
Published: March 2008

Abstract Platelet α2‐ and leucocyte β2‐adrenoceptors (as well as noradrenaline and adrenaline plasma levels) were studied in five patients with confirmed phaeochromocytoma using tritiated yohimbine and iodated cyanopindolol, respectively, before and after tumour removal. Patients with phaeochromocytoma had a lower leucocyte iodated cyanopindolol binding than control subjects, but no change in platelet tritiated yohimbine binding. Plasma catecholamine levels were higher than controls. Tumour removal induced a return to normal values of leucocyte iodated cyanopindolol binding and a decrease in plasma catecholamine levels. These results underline the potential interest of leucocyte β‐adrenoceptor quantification in the diagnosis and the follow‐up of phaeochromocytoma. Pharmacologically, they show that down‐regulation occurs in vivo for leucocyte β2‐adrenoceptors but not for platelet α2‐adrenoceptors.
Effect of cholestyramine on plasma cholecystokinin and pancreatic polypeptide levels, and exocrine pancreatic secretion
Authors: KOOP I. , FELLGIEBEL A. , KOOP H. , SCHAFMAYER A. , ARNOLD R.
Published: March 2008

Abstract The effect of acute and long‐term administration of cholestyramine, a non‐absorbable bile salt binding resin, on exocrine pancreatic secretion, plasma‐cholecystokinin (CCK) and plasma‐pancreatic polypeptide (PP) was investigated in 10 healthy volunteers. Oral ingestion of 12 g cholestyramine augmented the stimulatory effect of a liquid test meal on plasma‐CCK (3·5‐fold) and plasma‐PP (2‐fold). During prolonged treatment with 3 times 12 g cholestyramine daily for 4 weeks, the most pronounced increase in basal hormone levels was observed after 1 day, but progressively decreased during treatment and had normalized after 4 weeks. However, the stimulated plasma‐CCK output was still significantly elevated after cessation of treatment, compared with pretreatment values. After acute and chronic cholestyramine administration only stimulated lipase secretion was elevated, whereas trypsin and amylase remained unchanged. It is suggested that removal of bile salts enhances CCK and thereby PP release and pancreatic lipase secretion.
Binding sites for atrial natriuretic peptide on platelets in patients with congestive cardiomyopathy
Authors: STROM T. M. , WEIL J. , BRAUN F. , STANGL K. , TIMNIK A. , HEIM J. M. , GERZER R.
Published: March 2008

Abstract The aim of the present investigation was to evaluate a possible down‐regulation of atrial natriuretic peptide (ANP) binding sites on platelets in patients with chronically elevated ANP plasma levels. The assay procedure was proved to be able to measure the total number of binding sites even in the presence of high ANP plasma levels. We studied 15 adult patients with congestive cardiomyopathy in comparison to 18 healthy volunteers. In the patients the median ANP plasma level (median = 375, range: 155–900 pg ml‐1) was about six‐fold higher than in the healthy volunteers (median:55·5, range: 20–90 pg ml‐1). The median cyclic guanosine monophosphate (cGMP) plasma level (median:6·2, range: 2·5–21·4 pmol ml‐1) was about three‐fold higher than in the healthy volunteers (median: 1·8 range: 1–2·8 pmol ml‐1). Despite these markedly elevated ANP and cGMP plasma levels we did not find significantly less receptors per platelet in the patients (median: 19, range: 7·2–60·2) than in the healthy volunteers (median:24·5, range: 14·8–41·1). Furthermore, there was no difference in the dissociation constants between the patients (median: 10·5, range: 7·9–27·4 pmol l‐1) and the control subjects (median: 8·9, range: 5·4–17 pmol l‐1).
Localization of collagen mRNA in normal and scleroderma skin by in‐situ hybridization
Authors: SCHARFFETTER K. , LANKAT‐BUTTGEREIT B. , KRIEG T.
Published: March 2008

Abstract. Scleroderma is a fibrotic disease occurring in a localized or systemic form. Disturbed regulation of connective tissue metabolism plays an important role in its pathogenesis. However, until now, most of the data available were obtained from studies of fibroblasts in culture and there is considerable doubt that fibroblasts in a monolayer reflect the in‐vivo situation. Using in‐situ hybridization with specific antisense RNAs on frozen sections of skin, cells were detected displaying enhanced messenger RNA levels for type I and type III collagen in patients with localized and systemic scleroderma. Activated fibroblastic cells were often located near blood vessels in the deep dermis of patients with early stages of the disease and were mostly surrounded by mononuclear cells. These findings are in agreement with the concept that the interaction of fibroblasts with ‘immunocompetent cells’ is crucial in the initial activation of connective tissue metabolism in fibrosis.
Urinary excretion of bile acids during acute administration in man
Authors: SALVIOLI G. , LUGLI R. , PRADELLI J. M. , FRIGNANI ANNA , BOCCALLETTI VELIA
Published: March 2008

Abstract. Six healthy subjects, 45–72 years old, received a 10‐day feeding of 750 mg of two of the following bile acids: deoxycholate (DCA), chenodeoxycholate (CDCA), cholate (CA), hyodeoxycholate (HDCA), ursodeoxycholate (UDCA), and ursocholate (UCA). The urinary excretion of total bile acids was low during administration of lipophilic bile acids (DCA and CDCA), when serum levels show low postabsorption peaks. Instead, hydrophilic bile acids (UDCA and above all HDCA) were heavily excreted in the urine as sulphates and glucuronides, and serum levels reach high values. Only UCA, strongly hydrophilic, was predominantly excreted as unconjugated fractions. Thus, the physicochemical properties of bile acids (as measured by both the partition between octanol and water, and the water solubility) were factors that influenced the route of bile acid elimination from the body, whereas their conjugation was not always requested for urinary excretion.
Effects of sodium valproate on haem biosynthesis in man: implications for seizure management in the porphyric patient
Authors: McGUIRE G. M. , MACPHEE G. J. A. , THOMPSON G. G. , MOORE M. R. , BRODIE M. J.
Published: March 2008

Abstract. The short‐term effects of sodium valproate (VPA) on haem biosynthesis were assessed in a placebo‐controlled crossover trial in eight healthy male subjects who ingested VPA 500 mg t.i.d. and matched placebo for 5 days. All showed augmented activity of leucocyte 5‐aminolaevulinate synthase (ALA‐S) activity, the rate‐limiting enzyme of the haem biosynthetic pathway, following 3 and 5 days of VPA treatment (P<0·001). This was accompanied by increased urinary excretion of 5‐aminolaevulinic acid (ALA; P<0·02) and total porphyrins (P<0·01). Mean (± SD) total VPA concentrations on day 3 (89 ± 16 mg l‐1) and day 5 (91 ± 22 mg l‐1) were within the target range for the drug. The long‐term effects of VPA administration were examined in epileptic patients on established monotherapy. Leucocyte ALA‐S activity (P<0·001), and daily urinary excretion of porphobilinogen (P<0·01) and total porphyrins (P<0·01) were all higher than in age‐matched controls. No significant differences in erythrocyte ALA‐dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase activities were found between the groups. These data suggest that VPA is porphyrinogenic in man and cannot be recommended as safe for seizure management in the porphyric patient.
Effects of prolonged administration of two new α‐glucosidase inhibitors on blood glucose control, insulin requirements and breath hydrogen excretion in patients with insulin‐dependent diabetes mellitus
Authors: DIMITRIADIS G. , HATZIAGELAKI E. , LADAS S. , LINOS ATHENA , HILLEBRAND INGRID , RAPTIS S.
Published: March 2008

Abstract. Alpha‐glucosidase inhibitors delay carbohydrate absorption. In order to study the effects of two new α‐glucosidase inhibitors with long (BAYo1248) and short (BAYm1099) duration of action on glycaemic control, seventeen insulin‐dependent diabetics were connected to the Biostator® for 24 h and postprandial hyperglycaemia, insulin requirements and breath H2 concentrations were assessed under three conditions: (a) before administration of any α‐glucosidase inhibitor (control experiments), (b) after administration of BAYo1248 (40 mg before breakfast, nine patients) or BAYm1099 (100 mg before breakfast and dinner, eight patients) for 1 month, (c) after 1‐month administration of placebo (double‐blind crossover study). All patients were on standard diets (30 kcal kg‐1, 45% carbohydrate, 35% fat, 20% protein). BAYo1248 reduced postprandial hyperglycaemia and insulin requirements (vs. values in control and placebo experiments) after breakfast (124 ± 8 vs. 159 ± 8 and 158 ± 8 mg dl‐1, 16 ± 2 vs. 24 ± 4 and 23 ± 3 units, P<0·01) and lunch (138 ± 7 vs. 155 ± 11 and 162 ± 13 mg dl‐1, 19 ± 3 vs. 24 ± 3 and 23 ± 3 units, P<0·01) whereas BAYm1099 reduced postprandial hyperglycaemia and insulin requirements after breakfast (127 ± 4 vs. 167 ± 12 and 159 ± 6 mg dl‐1, 15 ± 3 vs. 24 ± 4 and 21 ± 3 units, P<0·02) and dinner (128 ± 4 vs. 169 ± 7 and 157 ± 10 mg dl‐1, 19 ± 2 vs. 28 ± 3 and 25 ± 2 units, P<0·01). Postprandial breath H2 concentrations were mildly increased when BAYo1248 and BAYm1099 were administered, compared with control and placebo experiments (BAYo1248:37 ± 5 vs. 9 ± 2 and 9 ± 4 ppm, BAYm1099 37 ± 10 vs. 9 ± 3 and 13 ± 3 ppm, P<0·05). In conclusion, improvement of glycaemic control, reduction of insulin requirements and virtual absence of malabsorption may make these agents useful adjuncts to insulin in the treatment of diabetes mellitus.